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87 results on '"MESH: Adipose Tissue"'

1. Identification of adipocytes as target cells for Leishmania infantum parasites

Author

Schwing, Aurélie, Pisani, Didier, Pomares, Christelle, Majoor, Alissa, Lacas-Gervais, Sandra, Jager, Jennifer, Lemichez, Emmanuel, Marty, Pierre, Boyer, Laurent, Michel, Grégory, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Aix Marseille Université (AMU), Laboratoire de PhysioMédecine Moléculaire (LP2M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), CCMA - Centre Commun de Microscopie Appliquée, Université Côte d'Azur (UCA), Toxines bactériennes - Bacterial Toxins, Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), We acknowledge financial support by the Conseil Départemental des Alpes-Maritimes and Conseil Régional PACA. This work was supported by a Grant from the Société Francophone du Diabète (SFD)/Pierre Fabre Médicament 2017., and DELARUE, NADINE

Subjects
Parasitic infection, Science, [SDV]Life Sciences [q-bio], MESH: Disease Susceptibility, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Article, Host-Parasite Interactions, Mice, MESH: Psychodidae, 3T3-L1 Cells, parasitic diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Adipocytes, Parasite immune evasion, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, MESH: Animals, Leishmania infantum, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, MESH: 3T3-L1 Cells, MESH: Leishmania infantum, [SDV] Life Sciences [q-bio], Disease Models, Animal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Adipose Tissue, MESH: Leishmaniasis, Visceral, Medicine, Leishmaniasis, Visceral, Disease Susceptibility, Psychodidae, MESH: Disease Models, Animal, MESH: Adipose Tissue
Abstract

International audience; Leishmania infantum is the causative agent of visceral leishmaniasis transmitted by the bite of female sand flies. According to the WHO, the estimated annual incidence of leishmaniasis is one million new cases, resulting in 30,000 deaths per year. The recommended drugs for treating leishmaniasis include Amphotericin B. But over the course of the years, several cases of relapses have been documented. These relapses cast doubt on the efficiency of actual treatments and raise the question of potential persistence sites. Indeed, Leishmania has the ability to persist in humans for long periods of time and even after successful treatment. Several potential persistence sites have already been identified and named as safe targets. As adipose tissue has been proposed as a sanctuary of persistence for several pathogens, we investigated whether Leishmania infantum could be found in this tissue. We demonstrated both in cell cultures and in vivo that Leishmania infantum was able to infect adipocytes. Altogether our results suggest adipocytes as a ‘safe target’ for Leishmania infantum parasites.

Published
2021

2. Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis

Author

Marie Maumus, Pauline Rozier, Florence Sabatier, Danièle Noël, Alexandre Thibault Jacques Maria, Christian Jorgensen, Claire Bony, Philippe Guilpain, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
systemic sclerosis, Adipose tissue, Cell Communication, MESH: Scleroderma, Systemic, MESH: Transforming Growth Factor beta1, Mice, Fibrosis, MESH: Animals, Biology (General), Myofibroblasts, skin and connective tissue diseases, Spectroscopy, integumentary system, anti-fibrotic, General Medicine, Phenotype, Pathophysiology, Computer Science Applications, Chemistry, Adipose Tissue, MESH: Fibrosis, Disease Susceptibility, medicine.symptom, extracellular vesicles, Myofibroblast, MESH: Adipose Tissue, MESH: Myofibroblasts, MESH: Immunophenotyping, QH301-705.5, MESH: Disease Susceptibility, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Article, Catalysis, Immunophenotyping, Transforming Growth Factor beta1, Inorganic Chemistry, MESH: Cell Communication, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Extracellular Vesicles, Physical and Theoretical Chemistry, MESH: Mice, Molecular Biology, QD1-999, mesenchymal stem cells, MESH: Humans, Scleroderma, Systemic, Organic Chemistry, Mesenchymal stem cell, TGFβ1, Fibroblasts, medicine.disease, MESH: Mesenchymal Stem Cells, Mechanism of action, MESH: Fibroblasts, MESH: Biomarkers, Cancer research, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers, Function (biology)
Abstract

International audience; Systemic sclerosis (SSc) is a complex disorder resulting from dysregulated interactions between the three main pathophysiological axes: fibrosis, immune dysfunction, and vasculopathy, with no specific treatment available to date. Adipose tissue-derived mesenchymal stromal cells (ASCs) and their extracellular vesicles (EVs) have proved efficacy in pre-clinical murine models of SSc. However, their precise action mechanism is still not fully understood. Because of the lack of availability of fibroblasts isolated from SSc patients (SSc-Fb), our aim was to determine whether a TGFβ1-induced model of human myofibroblasts (Tβ-Fb) could reproduce the characteristics of SSc-Fb and be used to evaluate the anti-fibrotic function of ASCs and their EVs. We found out that Tβ-Fb displayed the main morphological and molecular features of SSc-Fb, including the enlarged hypertrophic morphology and expression of several markers associated with the myofibroblastic phenotype. Using this model, we showed that ASCs were able to regulate the expression of most myofibroblastic markers on Tβ-Fb and SSc-Fb, but only when pre-stimulated with TGFβ1. Of interest, ASC-derived EVs were more effective than parental cells for improving the myofibroblastic phenotype. In conclusion, we provided evidence that Tβ-Fb are a relevant model to mimic the main characteristics of SSc fibroblasts and investigate the mechanism of action of ASCs. We further reported that ASC-EVs are more effective than parental cells suggesting that the TGFβ1-induced pro-fibrotic environment may alter the function of ASCs.

Published
2021

3. Management of Incidental Durotomy: Results from a Nationwide Survey Conducted by the French Society of Spine Surgery

Author

D'ASTORG, Henri, Szadkowski, Marc, Vieira, Thais Dutra, Dauzac, Cyril, Lonjon, Nicolas, Bougeard, Renaud, Litrico, Stephane, Dupuy, Martin, de Chirurgie du Rachis, Societe Francaise, Hôpital privé Jean-Mermoz [Lyon] (Ramsay-GDS), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Clinique du Val d'Ouest, Centre Hospitalier Universitaire de Nice (CHU Nice), and Clinique de l'Union

Subjects
MESH: Neurosurgeons, medicine.medical_treatment, Incidental durotomy, Computer-assisted web interviewing, Nationwide survey, Bed rest, MESH: Thrombin, 0302 clinical medicine, Spine surgery, Primary outcome, Surveys and Questionnaires, Supine Position, Medicine, Fascia, Practice Patterns, Physicians', Intraoperative Complications, Survey, MESH: Muscle, Skeletal, Thrombin, MESH: Tissue Adhesives, 3. Good health, Management, Drug Combinations, Adipose Tissue, Current management, 030220 oncology & carcinogenesis, MESH: Supine Position, MESH: Intraoperative Complications, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], France, Spinal surgery, MESH: Spine, MESH: Adipose Tissue, medicine.medical_specialty, MESH: Bed Rest, Fibrin Tissue Adhesive, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, MESH: Dura Mater, MESH: Suture Techniques, 03 medical and health sciences, MESH: Orthopedic Surgeons, Humans, MESH: Surveys and Questionnaires, Muscle, Skeletal, MESH: Drug Combinations, MESH: Fascia, MESH: Fibrin Tissue Adhesive, MESH: Humans, business.industry, Questionnaire, General surgery, Suture Techniques, Fibrinogen, Orthopedic Surgeons, Spine, MESH: France, Neurosurgeons, MESH: Fibrinogen, MESH: Practice Patterns, Physicians', Tissue Adhesives, Surgery, Dura Mater, Neurology (clinical), business, Bed Rest, 030217 neurology & neurosurgery, Continuous suture
Abstract

International audience; Objective: To obtain real-life data on the most common practices used for management of incidental durotomy (ID) in France.Methods: Data were collected from spinal surgeons using a practice-based online questionnaire. The survey comprised 31 questions on the current management of ID in France. The primary outcome was the identification of areas of consensus and uncertainty on ID follow-up.Results: A total of 217 surgeons (mainly orthopaedic surgeons and neurosurgeons) completed the questionnaire and were included in the analysis. There was a consensus on ID repair with 94.5% of the surgeons considering that an ID should always be repaired, if repairable, and 97.2% performing a repair if an ID occurred. The most popular techniques were simple suture or locked continuous suture (48.3% vs. 57.8% of surgeons). Nonrepairable IDs were more likely to be treated with surgical sealants than with an endogenous graft (84.9% vs. 75.5%). Almost two thirds of surgeons (71.6%) who adapted their standard postoperative protocol after an ID recommended bed rest in the supine position. Among these, 48.8% recommended 24 hours of bed rest, while 53.5% recommended 48 hours of bed rest. The surgeons considered that the main risk factors for ID were revision surgery (98.6%), patient's age (46.8%), surgeon's exhaustion (46.3%), and patient's weight (21.3%).Conclusions: This nationwide survey reflects the lack of a standardized management protocol for ID. Practices among surgeons remain very heterogeneous. Further consensus studies are required to develop a standard management protocol for ID.

Published
2020

4. Possible Role of Adipose Tissue and the Endocannabinoid System in Coronavirus Disease 2019 Pathogenesis: Can Rimonabant Return?

Author

Jérôme Ausseil, Stéphanie Trudel, Fabienne Briand-Mésange, Hugues Chap, Jean-Pierre Salles, Juliette Salles, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and PINIER, CHRISTINE

Subjects
MESH: Coronavirus, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Endocrinology, Diabetes and Metabolism, Adipose tissue, MESH: Endocannabinoids, Medicine (miscellaneous), 030209 endocrinology & metabolism, medicine.disease_cause, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rimonabant, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, MESH: COVID-19, MESH: Obesity, MESH: SARS-CoV-2, MESH: Respiration, Artificial, MESH: Prevalence, 030304 developmental biology, Coronavirus, 0303 health sciences, MESH: Severe Acute Respiratory Syndrome, MESH: Humans, Nutrition and Dietetics, biology, business.industry, MESH: Coronavirus Infections, biology.organism_classification, Endocannabinoid system, Virology, 3. Good health, MESH: Pandemics, MESH: Pneumonia, Viral, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Betacoronavirus, MESH: Rimonabant, business, Betacoronavirus, MESH: Adipose Tissue, medicine.drug
Abstract

International audience; This is the main conclusion of a recent study describing a strong relationship between the degree of obesity and the severity of COVID‐19 infection. Obesity has various negative consequences relative to the course of COVID‐19, including adverse effects on lung physiology, and induces comorbidities such as type II diabetes or hypertension. However, additional mechanisms involving the low‐grade inflammatory state accompanying obesity can also be suggested

Published
2020
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5. Adipose Tissue and Endocrine-Disrupting Chemicals: Does Sex Matter?

Author

Brigitte Le Magueresse-Battistoni, Le Magueresse-Battistoni, Brigitte, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and CarMeN, laboratoire

Subjects
Male, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, Adipose tissue, lcsh:Medicine, Review, Endocrine Disruptors, Bioinformatics, 0302 clinical medicine, estrogen, MESH: Obesity, Endocrine disrupting chemicals, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Sex Characteristics, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Endocrine Disruptors, 3. Good health, adipose tissue, [SDV] Life Sciences [q-bio], MESH: Environmental Pollutants, Environmental Pollutants, Female, MESH: Adipose Tissue, MESH: Sex Characteristics, Metabolic homeostasis, 030209 endocrinology & metabolism, Endocrine System, Biology, 03 medical and health sciences, medicine, Endocrine system, Humans, metabolic disorders, Obesity, MESH: Endocrine System, endocrine-disrupting chemicals, Chemical origin, 030304 developmental biology, Pollutant, MESH: Humans, Mechanism (biology), lcsh:R, Public Health, Environmental and Occupational Health, sex-dimorphism, medicine.disease, MESH: Male, 13. Climate action, glucocorticoid, MESH: Female, Hormone
Abstract

International audience; Obesity and metabolic-related diseases, among which diabetes, are prominent public health challenges of the 21st century. It is now well acknowledged that pollutants are a part of the equation, especially endocrine-disrupting chemicals (EDCs) that interfere with the hormonal aspect. The aim of the review is to focus on adipose tissue, a central regulator of energy balance and metabolic homeostasis, and to highlight the significant differences in the endocrine and metabolic aspects of adipose tissue between males and females which likely underlie the differences of the response to exposure to EDCs between the sexes. Moreover, the study also presents an overview of several mechanisms of action by which pollutants could cause adipose tissue dysfunction. Indeed, a better understanding of the mechanism by which environmental chemicals target adipose tissue and cause metabolic disturbances, and how these mechanisms interact and sex specificities are essential for developing mitigating and sex-specific strategies against metabolic diseases of chemical origin. In particular, considering that a scenario without pollutant exposure is not a realistic option in our current societies, attenuating the deleterious effects of exposure to pollutants by acting on the gut-adipose tissue axis may constitute a new direction of research.

Published
2020

6. Enhanced β-adrenergic signalling underlies an age-dependent beneficial metabolic effect of PI3K p110α inactivation in adipose tissue

Author

Araiz, Caroline, Yan, Anqi, Bettedi, Lucia, Samuelson, Sam, Virtue, Sam, McGavigan, Anne, Dani, Christian, Vidal-Puig, Antonio, Foukas, Lazaros, Samuelson, Isabella, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Samuelson, Isabella [0000-0001-8395-3090], Foukas, Lazaros C [0000-0002-6551-8789], and Apollo - University of Cambridge Repository

Subjects
MESH: Signal Transduction, Cell biology, Aging, Physiology, Class I Phosphatidylinositol 3-Kinases, MESH: Mice, Transgenic, Science, Mice, Transgenic, Article, Phosphatidylinositol 3-Kinases, Adrenergic Agents, Humans, Animals, MESH: Obesity, MESH: Animals, Obesity, lcsh:Science, [SDV.BDD]Life Sciences [q-bio]/Development Biology, MESH: Age Factors, Age Factors, MESH: Class I Phosphatidylinositol 3-Kinases, MESH: Insulin Resistance, Adipose Tissue, lcsh:Q, Insulin Resistance, MESH: Adipose Tissue, Signal Transduction
Abstract

The insulin/IGF-1 signalling pathway is a key regulator of metabolism and the rate of ageing. We previously documented that systemic inactivation of phosphoinositide 3-kinase (PI3K) p110α, the principal PI3K isoform that positively regulates insulin signalling, results in a beneficial metabolic effect in aged mice. Here we demonstrate that deletion of p110α specifically in the adipose tissue leads to less fat accumulation over a significant part of adult life and allows the maintenance of normal glucose tolerance despite insulin resistance. This effect of p110α inactivation is due to a potentiating effect on β-adrenergic signalling, which leads to increased catecholamine-induced energy expenditure in the adipose tissue. Our findings provide a paradigm of how partial inactivation of an essential component of the insulin signalling pathway can have an overall beneficial metabolic effect and suggest that PI3K inhibition could potentiate the effect of β-adrenergic agonists in the treatment of obesity and its associated comorbidities., Insulin/IGF-1 signalling plays an important role in the regulation of metabolism and ageing. Here the authors show that inactivation of the pathway component PI3K p110α in the adipose tissue of mice produces a beneficial metabolic effect by enhancing β-adrenergic signalling thus energy expenditure.

Published
2019

7. Lobular architecture of human adipose tissue defines the niche and fate of progenitor cells

Author

Christian Dani, A. Remaury, Jean Galitzky, Y. Veeranagouda, A. Briot, Anne Bouloumié, David Estève, M. Didier, Pauline Decaunes, Séverine Ledoux, Nathalie Boulet, Alexia Zakaroff-Girard, C. Belles, Jean-Claude Guillemot, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Sanofi Aventis R&D [Chilly-Mazarin], Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and boulet, nathalie

Subjects
0301 basic medicine, Cellular differentiation, [SDV]Life Sciences [q-bio], CD34, General Physics and Astronomy, Adipose tissue, 02 engineering and technology, chemistry.chemical_compound, MESH: Transforming Growth Factor beta1, MESH: Alkaline Phosphatase, Adipocyte, Adipocytes, MESH: Obesity, MESH: Nerve Tissue Proteins, Stem Cell Niche, lcsh:Science, Myofibroblasts, Multidisciplinary, Adipogenesis, Stem Cells, Cell Differentiation, 021001 nanoscience & nanotechnology, Cell biology, Extracellular Matrix, [SDV] Life Sciences [q-bio], Adipose Tissue, 0210 nano-technology, Fat metabolism, Myofibroblast, MESH: Adipose Tissue, MESH: Cell Differentiation, Stromal cell, MESH: Myofibroblasts, MESH: Stem Cell Niche, Science, Subcutaneous Fat, Nerve Tissue Proteins, MESH: Stem Cells, Receptors, Nerve Growth Factor, Biology, MESH: Extracellular Matrix, Intra-Abdominal Fat, General Biochemistry, Genetics and Molecular Biology, Article, Transforming Growth Factor beta1, 03 medical and health sciences, MESH: Receptors, Nerve Growth Factor, MESH: Subcutaneous Fat, Humans, Obesity, Progenitor cell, MESH: Intra-Abdominal Fat, MESH: Adipocytes, Progenitor, MESH: Humans, General Chemistry, Alkaline Phosphatase, 030104 developmental biology, chemistry, Mesenchymal stem cells, lcsh:Q, MESH: Adipogenesis
Abstract

Human adipose tissue (hAT) is constituted of structural units termed lobules, the organization of which remains to be defined. Here we report that lobules are composed of two extracellular matrix compartments, i.e., septa and stroma, delineating niches of CD45−/CD34+/CD31− progenitor subsets characterized by MSCA1 (ALPL) and CD271 (NGFR) expression. MSCA1+ adipogenic subset is enriched in stroma while septa contains mainly MSCA1−/CD271− and MSCA1−/CD271high progenitors. CD271 marks myofibroblast precursors and NGF ligand activation is a molecular relay of TGFβ-induced myofibroblast conversion. In human subcutaneous (SC) and visceral (VS) AT, the progenitor subset repartition is different, modulated by obesity and in favor of adipocyte and myofibroblast fate, respectively. Lobules exhibit depot-specific architecture with marked fibrous septa containing mesothelial-like progenitor cells in VSAT. Thus, the human AT lobule organization in specific progenitor subset domains defines the fat depot intrinsic capacity to remodel and may contribute to obesity-associated cardiometabolic risks., In human adipose tissue (AT), adipocytes are organized into units of lobules. Here the authors identify distinct fibrous septal and stromal compartments within AT lobules that differ in composition and potential between subcutaneous and visceral regions and are disturbed in obesity and metabolic syndrome.

Published
2019

8. Impact and Evolutionary Determinants of Neanderthal Introgression on Transcriptional and Post-Transcriptional Regulation

Author

Lluis Quintana-Murci, Martin Silvert, Maxime Rotival, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ED 515 - Complexité du vivant, Sorbonne Université (SU), This work was supported by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS), and the Agence Nationale de la Recherche (ANR) grants: 'IEIHSEER' ANR-14-CE14-0008-02 and 'TBPATHGEN' ANR-14-CE14-0007-02. The laboratory of L.Q.M. has received funding from the French government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10- LABX-62-IBEID). M.S. was funded by the Ecole Doctorale 'Complexité du vivant,' Sorbonne Université (contract n°2532/2016)., ANR-14-CE14-0008,IEIHSEER,L'encéphalite Herpétique de l'enfant résulte de déficits héréditaires d'immunité contre l'HSV-1: une exception ou une règle?(2014), ANR-14-CE14-0007,TBPATHGEN,Dissection de la pathogenèse de la tuberculose par l'identification de défauts monogéniques de l'immunité dans les formes pédiatriques sévères de la maladie(2014), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Neanderthal, Transcription, Genetic, MESH: Selection, Genetic, T-Lymphocytes, promoters, adaptation, Genome, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, MESH: Animals, RNA Processing, Post-Transcriptional, Genetics (clinical), MESH: Evolution, Molecular, Neanderthals, MESH: Neanderthals, Regulation of gene expression, Recombination, Genetic, 0303 health sciences, Adipogenesis, MESH: Genomics, MESH: Polymorphism, Single Nucleotide, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Gene Expression Regulation, Developmental, Genomics, Adaptation, Physiological, Adipose Tissue, Regulatory sequence, miRNAs, MESH: Recombination, Genetic, MESH: Adipose Tissue, MESH: RNA Processing, Post-Transcriptional, Introgression, Biology, Polymorphism, Single Nucleotide, Evolution, Molecular, 03 medical and health sciences, biology.animal, Report, Genetics, Animals, Humans, Selection, Genetic, Enhancer, Post-transcriptional regulation, MESH: Genome, Human, 030304 developmental biology, MESH: Humans, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Genome, Human, T-cells, MESH: Transcription, Genetic, immunity, MESH: Adaptation, Physiological, MicroRNAs, MESH: T-Lymphocytes, Evolutionary biology, enhancers, archaic introgression, Adaptation, gene regulation, MESH: Adipogenesis, MESH: MicroRNAs, 030217 neurology & neurosurgery
Abstract

Archaic admixture is increasingly recognized as an important source of diversity in modern humans, with Neanderthal haplotypes covering 1-3% of the genome of present-day Eurasians. Recent work has shown that archaic introgression has contributed to human phenotypic diversity, mostly through the regulation of gene expression. Yet, the mechanisms through which archaic variants alter gene expression, and the forces driving the introgression landscape at regulatory regions remain elusive. Here, we explored the impact of archaic introgression on transcriptional and post-transcriptional regulation, focusing on promoters and enhancers across 127 different tissues as well as microRNA-mediated regulation. Although miRNAs themselves harbor few archaic variants, we found that some of these variants may have a strong impact on miRNA-mediated gene regulation. Enhancers were by far the regulatory elements most affected by archaic introgression, with one third of the tissues tested presenting significant enrichments. Specifically, we found strong enrichments of archaic variants in adipose-related tissues and primary T cells, even after accounting for various genomic and evolutionary confounders such as recombination rate and background selection. Interestingly, we identified signatures of adaptive introgression at enhancers of some key regulators of adipogenesis, raising the interesting hypothesis of a possible adaptation of early Eurasians to colder climates. Collectively, this study sheds new light onto the mechanisms through which archaic admixture have impacted gene regulation in Eurasians and, more generally, increases our understanding of the contribution of Neanderthals to the regulation of acquired immunity and adipose homeostasis in modern humans.

Published
2019

9. Small non coding RNAs in adipocyte biology and obesity

Author

Ez-Zoubir Amri, Marcel Scheideler, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Adipocytes, White, Adipose tissue, Type 2 diabetes, MESH: Energy Intake, Bioinformatics, Biochemistry, Endocrinology, RNA, Transfer, Gene expression, MESH: Obesity, MESH: Animals, Small nucleolar RNA, MESH: Adipocytes, Brown, Adipogenesis, Adipocyte, microRNA, Non-coding RNA, MESH: Gene Expression Regulation, 3. Good health, Adipocytes, Brown, Adipose Tissue, MESH: Adipose Tissue, MESH: RNA, Small Nucleolar, Biology, snoRNA, 03 medical and health sciences, medicine, Animals, Humans, RNA, Small Nucleolar, Obesity, Molecular Biology, tRNA, Small non-coding RNA, MESH: Humans, Small Non-coding Rna, Microrna, Snorna, Trna, medicine.disease, MESH: RNA, Transfer, MESH: Adipocytes, White, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, MESH: Biomarkers, Human genome, Energy Intake, MESH: Adipogenesis, MESH: MicroRNAs, Biomarkers, Function (biology)
Abstract

International audience; Obesity has reached epidemic proportions world-wide and constitutes a substantial risk factor for hypertension, type 2 diabetes, cardiovascular diseases and certain cancers. So far, regulation of energy intake by dietary and pharmacological treatments has met limited success. The main interest of current research is focused on understanding the role of different pathways involved in adipose tissue function and modulation of its mass. Whole-genome sequencing studies revealed that the majority of the human genome is transcribed, with thousands of non-protein-coding RNAs (ncRNA), which comprise small and long ncRNAs. ncRNAs regulate gene expression at the transcriptional and post-transcriptional level. Numerous studies described the involvement of ncRNAs in the pathogenesis of many diseases including obesity and associated metabolic disorders. ncRNAs represent potential diagnostic biomarkers and promising therapeutic targets. In this review, we focused on small ncRNAs involved in the formation and function of adipocytes and obesity.

Published
2017

10. Body fat distribution in Parkinson's disease: An MRI-based body fat quantification study

Author

Jan Kassubek, Albert C. Ludolph, Hans-Peter Müller, Denise Bernhardt, Luc Dupuis, University of Ulm (UUlm), Heidelberg Institute of Radiation Oncology [Heidelberg, Germany] (HIRO), Heidelberg University Hospital [Heidelberg], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dieterle, Stéphane

Subjects
Leptin, Male, Parkinson's disease, [SDV]Life Sciences [q-bio], Statistics as Topic, Adipose tissue, Gastroenterology, Weight loss, Body Mass Index, MESH: Magnetic Resonance Imaging, [SCCO]Cognitive science, 0302 clinical medicine, MESH: Sequestosome-1 Protein, Image Processing, Computer-Assisted, Medicine, Mass index, 030212 general & internal medicine, MESH: Statistics, Nonparametric, medicine.diagnostic_test, MESH: Peptides, Parkinson Disease, MESH: Follow-Up Studies, MESH: Case-Control Studies, MESH: Image Processing, Computer-Assisted, [SDV] Life Sciences [q-bio], Adipose Tissue, Neurology, Female, medicine.symptom, MESH: Adipose Tissue, medicine.medical_specialty, Body fat distribution, MESH: Zebrafish Proteins, Statistics, Nonparametric, MESH: Protein-Serine-Threonine Kinases, MESH: Body Mass Index, 03 medical and health sciences, Magnetic resonance imaging, Internal medicine, Humans, MESH: Body Fat Distribution, MESH: Zebrafish, MESH: Statistics as Topic, MESH: Humans, MESH: Phosphorylation, business.industry, Body Weight, Case-control study, [SCCO] Cognitive science, MESH: Leptin, medicine.disease, MESH: Male, MESH: Body Weight, Endocrinology, Metabolism, Case-Control Studies, Neurology (clinical), Geriatrics and Gerontology, business, Body mass index, MESH: Female, 030217 neurology & neurosurgery, MESH: Parkinson Disease, Follow-Up Studies
Abstract

International audience; Introduction: There is some evidence that Parkinson's Disease (PD) patients have lower body weight and lower fat mass when compared to healthy subjects and that lower body weight and fat mass influence disease risk and progression. It remains unclear, however, if weight loss of fat mass loss occurs only in a subgroup of patients and whether fat distribution is altered during PD. The aim of this study was to prospectively investigate adipose tissue content and distribution in PD patients.Methods: The body fat composition of PD patients (N = 54) was compared with age matched healthy controls (N = 55) using a magnetic resonance imaging (MRI)-based method. A longitudinal MRI scan was acquired in 25 PD patients after a mean follow up period of 12 months.Results: The volume of total body fat as well as of visceral fat showed no difference between PD patients and healthy controls at baseline or at follow up. However, PD patients displayed decreased subcutaneous fat tissue (p = 0.01) and a higher visceral to subcutaneous fat ratio as compared to controls (p = 0.004). After follow up, 16 PD patients did not lose weight, while 9 PD patients lost between 0.5 and 10 kg.Conclusion: Fat distribution is altered in PD patients, with an increased ratio of visceral to subcutaneous fat.

Published
2016

11. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment

Author

Mathieu Bergé, Aurélie Waget, Philippe J. Sansonetti, Natalia F. Smirnova, Thierry Sulpice, Rémy Burcelin, Philippe Langella, Luis G. Bermúdez-Humarán, Nina Rautonen, Christelle Vachoux, Jacques Amar, Pascale Klopp, Chantal Chabo, Arthur C. Ouwehand, Sampo J. Lahtinen, Service d'hypertension artérielle et thérapeutique [CHU Toulouse] (HTA et thérapeutique), Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Unité de recherche d'Écologie et Physiologie du Système Digestif (UEPSD), Institut National de la Recherche Agronomique (INRA), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Adhésion Bacterienne et Formation de Biofilms, PRES Université de Toulouse, Physiogenex, DuPont Health & Nutrition, Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), Agence Nationale de la Recherche (ANR Floradip, Transflora, Vaiomer), European Commission [241913], Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne et Hypertension Artérielle [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Unité d'Ecologie et de Physiologie du Système Digestif, INRA, Unité d'écologie et de physiologie du système digestif, Laboratoire de microbiologie et génétique moléculaires (LMGM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Chaire Microbiologie et Maladies infectieuses

Subjects
Bifidobacterium lactis 420, obesity, MESH: Bifidobacterium, [SDV]Life Sciences [q-bio], Lipopolysaccharide Receptors, M CELLS, MESH: Nod1 Signaling Adaptor Protein, Adipose tissue, Chromosomal translocation, Bacteremia, INDUCED INFLAMMATION, Type 2 diabetes, MESH: Mice, Knockout, Bacterial Adhesion, law.invention, Probiotic, Mice, 0302 clinical medicine, law, Nod1 Signaling Adaptor Protein, IMMUNE-RESPONSE, MESH: Animals, Intestinal Mucosa, MESH: Bacteremia, pathogen-associated molecular pattern receptors, 2. Zero hunger, Mice, Knockout, 0303 health sciences, biology, diabetes, MESH: Escherichia coli, MESH: Antigens, CD14, GUT MICROBIOTA, 3. Good health, Bifidobacterium animalis, [SDV] Life Sciences [q-bio], ADIPOSE-TISSUE, Blood, Adipose Tissue, ESCHERICHIA-COLI, MESH: Intestinal Mucosa, inflammation, INDUCED INSULIN-RESISTANCE, HIGH-FAT-DIET, INNATE IMMUNITY, OBESE MICE, Molecular Medicine, medicine.symptom, MESH: Adipose Tissue, MESH: Bacterial Translocation, MESH: Diabetes Mellitus, Type 2, MESH: Myeloid Differentiation Factor 88, Research Article, CD14, 030209 endocrinology & metabolism, Inflammation, Diet, High-Fat, Microbiology, 03 medical and health sciences, Insulin resistance, MESH: Mice, Inbred C57BL, MESH: Blood, medicine, Escherichia coli, Animals, MESH: Bacterial Adhesion, MESH: Mice, 030304 developmental biology, Probiotics, medicine.disease, biology.organism_classification, Mice, Inbred C57BL, MESH: Diet, High-Fat, Diabetes Mellitus, Type 2, Bacterial Translocation, Immunology, Myeloid Differentiation Factor 88, Bifidobacterium, MESH: Probiotics
Abstract

International audience; A fat-enriched diet modifies intestinal microbiota and initiates a low-grade inflammation, insulin resistance and type-2 diabetes. Here, we demonstrate that before the onset of diabetes, after only one week of a high-fat diet (HFD), live commensal intestinal bacteria are present in large numbers in the adipose tissue and the blood where they can induce inflammation. This translocation is prevented in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but overtly increased in Myd88 knockout and ob/ob mouse. This 'metabolic bacteremia' is characterized by an increased co-localization with dendritic cells from the intestinal lamina propria and by an augmented intestinal mucosal adherence of non-pathogenic Escherichia coli. The bacterial translocation process from intestine towards tissue can be reversed by six weeks of treatment with the probiotic strain Bifidobacterium animalis subsp. lactis 420, which improves the animals' overall inflammatory and metabolic status. Altogether, these data demonstrate that the early onset of HFD-induced hyperglycemia is characterized by an increased bacterial translocation from intestine towards tissues, fuelling a continuous metabolic bacteremia, which could represent new therapeutic targets.

Published
2011

12. Adipose Tissue Endothelial Cells From Obese Human Subjects: Differences Among Depots in Angiogenic, Metabolic, and Inflammatory Gene Expression and Cellular Senescence

Author

Aurélie Villaret, Tamara Tchkonia, Patrick Chiotasso, Coralie Sengenès, James L. Kirkland, David Estève, Marie Adeline Marques, Max Lafontan, Pauline Decaunes, Jean Galitzky, Anne Bouloumié, Laboratoires Sérobiologiques, Division of Cognis, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chirurgie Générale et Digestive [Rangueil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Robert and Arlene Kogod Center on Aging, Mayo Clinic, and Simon, Marie Francoise

Subjects
MESH: Inflammation, Male, CD31, Endothelial lipase, Biopsy, Endocrinology, Diabetes and Metabolism, Adipose tissue, 030204 cardiovascular system & hematology, MESH: Hypertension, Body Mass Index, MESH: Biopsy, 0302 clinical medicine, Reference Values, Adipocytes, MESH: Obesity, Cellular Senescence, 0303 health sciences, MESH: Middle Aged, MESH: Reference Values, MESH: Hypercholesterolemia, Middle Aged, MESH: Gene Expression Regulation, Immunohistochemistry, Endothelial stem cell, Vascular endothelial growth factor A, MESH: Cell Aging, Adipose Tissue, Hypertension, Female, medicine.symptom, tissues, Cell aging, MESH: Adipose Tissue, Adult, medicine.medical_specialty, Hypercholesterolemia, Subcutaneous Fat, Inflammation, Intra-Abdominal Fat, Biology, MESH: Body Mass Index, Proinflammatory cytokine, 03 medical and health sciences, MESH: Subcutaneous Fat, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Internal Medicine, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, MESH: Intra-Abdominal Fat, MESH: Adipocytes, 030304 developmental biology, MESH: Humans, Chemokine CCL20, nutritional and metabolic diseases, MESH: Immunohistochemistry, MESH: Adult, MESH: Chemokine CCL20, MESH: Male, Metabolism, Endocrinology, Gene Expression Regulation, MESH: Female
Abstract

OBJECTIVE Regional differences among adipose depots in capacities for fatty acid storage, susceptibility to hypoxia, and inflammation likely contribute to complications of obesity. We defined the properties of endothelial cells (EC) isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) biopsied in parallel from obese subjects. RESEARCH DESIGN AND METHODS The architecture and properties of the fat tissue capillary network were analyzed using immunohistochemistry and flow cytometry. CD34+/CD31+ EC were isolated by immunoselection/depletion. Expression of chemokines, adhesion molecules, angiogenic factor receptors, as well as lipogenic and senescence-related genes were assayed by real-time PCR. Fat cell size and expression of hypoxia-dependent genes were determined in adipocytes from both fat depots. RESULTS Hypoxia-related genes were more highly expressed in VAT than SAT adipocytes. VAT adipocytes were smaller than SAT adipocytes. Vascular density and EC abundance were higher in VAT. VAT-EC exhibited a marked angiogenic and inflammatory state with decreased expression of metabolism-related genes, including endothelial lipase, GPIHBP1, and PPAR gamma. VAT-EC had enhanced expression of the cellular senescence markers, IGFBP3 and γ-H2AX, and decreased expression of SIRT1. Exposure to VAT adipocytes caused more EC senescence-associated β-galactosidase activity than SAT adipocytes, an effect reduced in the presence of vascular endothelial growth factor A (VEGFA) neutralizing antibodies. CONCLUSIONS VAT-EC exhibit a more marked angiogenic and proinflammatory state than SAT-EC. This phenotype may be related to premature EC senescence. VAT-EC may contribute to hypoxia and inflammation in VAT.

Published
2010
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13. An intervention study of the effects of calcium intake on faecal fat excretion, energy metabolism and adipose tissue mRNA expression of lipid-metabolism related proteins

Author

Jos H. C. H. Stegen, Carine Valle, Niels Boon, Nathalie Viguerie, Gabby B. Hul, Wendy E. Sluijsmans, Dominique Langin, Wim H. M. Saris, Nutrition and Toxicology Research Institute, Maastricht University [Maastricht], Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Department of Human Biology (NUTRIM), Maastricht University [Maastricht]-Nutrition and Toxicology Research Institute Maastricht, Simon, Marie Francoise, Humane Biologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, and RS: NUTRIM - R1 - Metabolic Syndrome

Subjects
Male, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Adipose tissue, MESH: Food Habits, MESH: Energy Intake, MESH: Fatty Acid Synthetase Complex, Feces, MESH: Reverse Transcriptase Polymerase Chain Reaction, Gene expression, Adipocytes, MESH: Lipid Metabolism, Regulation of gene expression, Nutrition and Dietetics, Cross-Over Studies, Chemistry, Reverse Transcriptase Polymerase Chain Reaction, MESH: Energy Metabolism, MESH: Feces, MESH: Gene Expression Regulation, Adipose Tissue, Female, MESH: Calorimetry, Indirect, MESH: Calcium, Dietary, MESH: Adipose Tissue, MESH: Triglycerides, Adult, medicine.medical_specialty, chemistry.chemical_element, Calcium, MESH: Cross-Over Studies, Excretion, MESH: Diet, Internal medicine, medicine, Humans, RNA, Messenger, MESH: Adipocytes, Triglycerides, MESH: RNA, Messenger, Messenger RNA, MESH: Humans, MESH: Adult, Lipid metabolism, Calorimetry, Indirect, Feeding Behavior, medicine.disease, Lipid Metabolism, Obesity, MESH: Male, Diet, Calcium, Dietary, Endocrinology, Gene Expression Regulation, Fatty Acid Synthases, Energy Intake, Energy Metabolism, MESH: Female
Abstract

Context:In various observational studies, an inverse relation between calcium intake and body weight has been observed. A possible explanation could be an increased calcium excretion through the faeces caused by an increased dietary calcium intake.Objective:To examine whether an increased calcium intake could lead to changes in faecal fat and energy excretion.Design:Four different isocaloric diets with various calcium contents (400, 1200 and 2500 mg from dairy and 1200 mg from calcium carbonate (1200S)) were administered in a crossover design for 7 days each.Subjects:Five healthy men and five healthy women (age=28+/-2, body mass index=24.1+/-0.4, body fat%=25.6+/-2.4) were recruited by local announcement.Measurements:At the end of every intervention period, faecal samples were collected for determination of fat, energy and calcium content, blood samples were obtained for determination of relevant blood parameters; and fat samples were obtained for measurement of the mRNA expression. Furthermore, resting energy expenditure and fat oxidation were measured with the ventilated-hood technique.Results:We observed a non-significant 56% increase in fat excretion (P=0.159) on the 2500 mg diet, compared to the 400 mg diet. The 2500 mg diet significantly reduced the expression of fatty acid synthase (FAS) mRNA (P

Published
2007

14. Adipose TriGlyceride Lipase (ATGL) and Hormone-Sensitive Lipase (HSL) protein expression is decreased in the obese insulin resistant state

Author

Carine Valle, Egbert F. Smit, Ellen E. Blaak, Peter Arner, Wim H. M. Saris, Johan W. E. Jocken, Dominique Langin, Cecilia Holm, Gabby B. Hul, Humane Biologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: NUTRIM - R1 - Metabolic Syndrome, Department of Human Biology, Nutrition and Toxicology, Maastricht University [Maastricht]-Research Institute Maastricht, Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Division of Diabetes, Metabolism, and Endocrinology, Lund University [Lund], Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], This study has received support from NUGENOB (Nutrient-Gene Interaction in Human Obesity, Implications for Dietary Guidelines) supported by the European Commission (Contract QLK1-CT-2000-00618), HEPADIP (Hepatic and Adipose Tissue and Functions in the Metabolic Syndrome) supported by the European Commission as an integrated project under the 6th Framework Programme (Contract LSHM-CT-2005- 018734), and Swedish Research Council Project 112 84., European Project: 32591,HEPADIP, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], University of Lund, Simon, Marie Francoise, Hepatic and adipose tissue and functions in the metabolic syndrome - HEPADIP - 32591 - OLD, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Biopsy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Adipose tissue, Hormone-sensitive lipase, MESH: Regression Analysis, Biochemistry, MESH: Lipase, MESH: Biopsy, 0302 clinical medicine, Endocrinology, Hyperinsulinemia, MESH: Obesity, MESH: Diet, Reducing, 2. Zero hunger, 0303 health sciences, MESH: Middle Aged, MESH: Sterol Esterase, MESH: Gene Expression Regulation, Enzymologic, Leptin, food and beverages, Middle Aged, MESH: Insulin Resistance, Adipose Tissue, MESH: Hyperinsulinism, Regression Analysis, Female, MESH: Adipose Tissue, Adult, medicine.medical_specialty, Diet, Reducing, 030209 endocrinology & metabolism, Biology, Gene Expression Regulation, Enzymologic, MESH: Weight Loss, 03 medical and health sciences, Insulin resistance, Hyperinsulinism, Internal medicine, Weight Loss, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, RNA, Messenger, MESH: RNA, Messenger, 030304 developmental biology, MESH: Humans, Insulin, Biochemistry (medical), MESH: Adult, Lipase, Sterol Esterase, medicine.disease, MESH: Male, Adipose triglyceride lipase, Insulin Resistance, MESH: Female
Abstract

International audience; AIM/HYPOTHESIS: Obesity is associated with increased triacylglycerol (TAG) storage in adipose tissue and insulin resistance. The mobilization of stored TAG is mediated by hormone-sensitive lipase (HSL) and the recently discovered adipose triglyceride lipase (ATGL). The aim of the present study was to examine whether ATGL and HSL mRNA and protein expression are altered in insulin-resistant conditions. In addition, we investigated whether a possible impaired expression could be reversed by a period of weight reduction. METHODS: Adipose tissue biopsies were taken from obese subjects (n = 44) with a wide range of insulin resistance, before and just after a 10-wk hypocaloric diet. ATGL and HSL protein and mRNA expression was determined by Western blot and quantitative RT-PCR, respectively. RESULTS: Fasting insulin levels and the degree of insulin resistance (using the homeostasis model assessment index for insulin resistance) were negatively correlated with ATGL and HSL protein expression, independent of age, gender, fat cell size, and body composition. Both mRNA and protein levels of ATGL and HSL were reduced in insulin-resistant compared with insulin-sensitive subjects (P < 0.05). Weight reduction significantly decreased ATGL and HSL mRNA and protein expression. A positive correlation between the decrease in leptin and the decrease in ATGL protein level after weight reduction was observed. Finally, ATGL and HSL mRNA and protein levels seem to be highly correlated, indicating a tight coregulation and transcriptional control. CONCLUSIONS: In obese subjects, insulin resistance and hyperinsulinemia are strongly associated with ATGL and HSL mRNA and protein expression, independent of fat mass. Data on weight reduction indicated that also other factors (e.g. leptin) relate to ATGL and HSL protein expression.

Published
2007

15. CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice

Author

Poggi, M, Morin, M, Bastelica, D, Govers, R, Canault, M, Bernot, D, Georgelin, O, Verdier, M, Burcelin, R, Olive, D, Alessi, Marie-Christine, Peiretti, F, Nunès, J A, Poggi, F, Morin, Fanny, Bastelica, F, Govers, F, Canault, F, Bernot, F, Georgelin, F, Verdier, François, Burcelin, F, Olive, F, Alessi, F, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche sur l'Enseignement et l'Apprentissage des Sciences (CREAS), Université de Sherbrooke [Sherbrooke], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Génie des procédés frigorifiques (UR GPAN), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Phytopathology, Wageningen University and Research Centre [Wageningen] (WUR), Francecol Technology, EA 4279 Laboratoire Physiologie des Fruits et Légumes, Avignon Université (AU), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Sherbrooke (UdeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Wageningen University and Research [Wageningen] (WUR), Societe Francophone du Diabete, European society of cardiology, Comite du Var de la Ligue contre le cancer, Fondation pour la Recherche Medicale [Equipe FRM DEQ20140329534], Aix-Marseille Universite, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de la Méditerranée - Aix-Marseille 2 - Institut National de la Recherche Agronomique (INRA) - Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Institut Paoli-Calmettes - Aix Marseille Université (AMU), and Université Paul Sabatier - Toulouse 3 (UPS) - Hôpital de Rangueil - Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Inflammation, MESH: Antigens, CD28, Endocrinology, Diabetes and Metabolism, MESH: Antigens, CD27, Medicine (miscellaneous), Adipose tissue, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: Mice, Knockout, Mice, MESH: Obesity, MESH: Animals, MESH: Fatty Liver, ComputingMilieux_MISCELLANEOUS, MESH: Lipid Metabolism, Mice, Knockout, Nutrition and Dietetics, biology, Chemistry, Intracellular Signaling Peptides and Proteins, CD28, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Insulin Resistance, Adipose Tissue, Liver, medicine.symptom, MESH: Adipose Tissue, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Inflammation, chemical and pharmacologic phenomena, Proinflammatory cytokine, Insulin resistance, CD28 Antigens, MESH: Mice, Inbred C57BL, Internal medicine, MESH: Intracellular Signaling Peptides and Proteins, medicine, Animals, Obesity, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Mice, Adiponectin, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Lipid Metabolism, medicine.disease, MESH: Male, Tumor Necrosis Factor Receptor Superfamily, Member 7, Fatty Liver, Mice, Inbred C57BL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Disease Models, Animal, Endocrinology, MESH: Gene Deletion, biology.protein, Insulin Resistance, Steatosis, MESH: Disease Models, Animal, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Gene Deletion, GLUT4, MESH: Liver
Abstract

International audience; Lymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown.During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions.Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation.Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis.

Published
2015

16. Antagonistic functions of LMNA isoforms in energy expenditure and lifespan

Author

Jamal Tazi, Marion de Toledo, Isabel C. Lopez-Mejia, Philippe Fort, Ez-Zoubir Amri, Guillaume E. Beranger, Laure Lapasset, Celia Lopez-Herrera, François Casas, Patricia Cavelier, Karim Chebli, Lluis Fajas, Carine Chavey, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Lausanne (UNIL), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS), U844, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
MESH: Signal Transduction, MESH: Protein Precursors, [SDV]Life Sciences [q-bio], Gβ phosphorylation, Gene Expression, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: Protein Isoforms, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Biochemistry, Chemotropism, LMNA, Transcriptome, Mice, Progeria, energy expenditure, Adipocytes, Protein Isoforms, MESH: Aging, MESH: Animals, [SDV.BDD]Life Sciences [q-bio]/Development Biology, MESH: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Cells, Cultured, integumentary system, MESH: Alternative Splicing, MESH: Energy Metabolism, Nuclear Proteins, mammifère, MESH: Transcription Factors, Yeast mating response, Lamin Type A, Progerin, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Cell biology, mitochondria, Adipose Tissue, MESH: Longevity, LMNA protein, mitochondrie, protéine, embryonic structures, Intercellular Signaling Peptides and Proteins, MESH: Adipose Tissue, MESH: Cells, Cultured, Signal Transduction, Gene isoform, congenital, hereditary, and neonatal diseases and abnormalities, MESH: Gene Expression, MESH: Lamin Type A, MESH: Mice, Transgenic, MESH: Mitochondria, MESH: Progeria, Longevity, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Saccharomyces cerevisiae, Reorientation, Biology, mitochondria biogenesis, Genetics, medicine, Animals, mammals, Protein Precursors, MESH: Intercellular Signaling Peptides and Proteins, MESH: Mice, Molecular Biology, MESH: Adipocytes, Adaptor Proteins, Signal Transducing, énergie métabolisable, Scientific Reports, Alternative splicing, aging, isoforms, nutritional and metabolic diseases, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Polarized growth, medicine.disease, Molecular biology, Hot off the Press, Alternative Splicing, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Mitochondrial biogenesis, RNA processing, Energy Metabolism, protein, MESH: Nuclear Proteins, Lamin, Transcription Factors
Abstract

International audience; Alternative RNA processing of LMNA pre-mRNA produces three main protein isoforms, that is, lamin A, progerin, and lamin C. De novo mutations that favor the expression of progerin over lamin A lead to Hutchinson-Gilford progeria syndrome (HGPS), providing support for the involvement of LMNA processing in pathological aging. Lamin C expression is mutually exclusive with the splicing of lamin A and progerin isoforms and occurs by alternative polyadenylation. Here, we investigate the function of lamin C in aging and metabolism using mice that express only this isoform. Intriguingly, these mice live longer, have decreased energy metabolism, increased weight gain, and reduced respiration. In contrast, progerin-expressing mice show increased energy metabolism and are lipodystrophic. Increased mitochondrial biogenesis is found in adipose tissue from HGPS-like mice, whereas lamin C-only mice have fewer mitochondria. Consistently, transcriptome analyses of adipose tissues from HGPS and lamin C-only mice reveal inversely correlated expression of key regulators of energy expenditure, including Pgc1a and Sfrp5. Our results demonstrate that LMNA encodes functionally distinct isoforms that have opposing effects on energy metabolism and lifespan in mammals.

Published
2014

17. Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy homeostasis and increased physical activity in mice

Author

Audrey Toulotte, Françoise Rohner-Jeanrenaud, Valerie M. Schwitzgebel, Petra Susan Hüppi, Emmanuel Somm, Christelle Veyrat-Durebex, Audrey Guérardel, Uwe Maskos, Kamel Maouche, Université de Genève = University of Geneva (UNIGE), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie intégrative des Systèmes cholinergiques (NISC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Valérie M. Schwitzgebel received a research grant from the Gertrude von Meissner foundation and Emmanuel Somm was supported by the University of Geneva and the 'Fondation pour Recherches Médicales (TULIPE)'., We thank Laurent Depret and Damien Favrichon (Charles River FRANCE) for assistance in mice cohort management, Déborah Aeberhard for technical assistance, and Nicolas Bonnet and Serge Ferrari for access to DEXA measurement., University of Geneva [Switzerland], Neurobiologie intégrative des Systèmes cholinergiques, and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Adipose tissue, Receptors, Nicotinic, Biochemistry, MESH: Mice, Knockout, Energy homeostasis, chemistry.chemical_compound, Mice, [SCCO]Cognitive science, 0302 clinical medicine, Endocrinology, Adipocyte, Insulin Secretion, Insulin, MESH: Animals, Mice, Knockout, 0303 health sciences, ddc:618, Diabetes, MESH: Motor Activity, MESH: Glucose, Nicotinic agonist, medicine.anatomical_structure, Adipose Tissue, MESH: Receptors, Nicotinic, MESH: Adipose Tissue, Islet, medicine.medical_specialty, MESH: Insulin, Biology, Motor Activity, nAChR, 03 medical and health sciences, Islets of Langerhans, Insulin resistance, MESH: Mice, Inbred C57BL, Internal medicine, Genetics, medicine, Animals, Humans, Obesity, ddc:612, Molecular Biology, MESH: Mice, 030304 developmental biology, Acetylcholine receptor, MESH: Humans, Pancreatic islets, MESH: Islets of Langerhans, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, MESH: Male, Mice, Inbred C57BL, Glucose, chemistry, Glycemic Index, MESH: Glycemic Index, 030217 neurology & neurosurgery
Abstract

International audience; Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels well characterized in neuronal signal transmission. Moreover, recent studies have revealed nAChR expression in nonneuronal cell types throughout the body, including tissues involved in metabolism. In the present study, we screen gene expression of nAChR subunits in pancreatic islets and adipose tissues. Mice pancreatic islets present predominant expression of α7 and β2 nAChR subunits but at a lower level than in central structures. Characterization of glucose and energy homeostasis in α7β2nAChR(-/-) mice revealed no major defect in insulin secretion and sensitivity but decreased glycemia apparently unrelated to gluconeogenesis or glycogenolysis. α7β2nAChR(-/-) mice presented an increase in lean and bone body mass and a decrease in fat storage with normal body weight. These observations were associated with elevated spontaneous physical activity in α7β2nAChR(-/-) mice, mainly due to elevation in fine vertical (rearing) activity while their horizontal (ambulatory) activity remained unchanged. In contrast to α7nAChR(-/-) mice presenting glucose intolerance and insulin resistance associated to excessive inflammation of adipose tissue, the present metabolic phenotyping of α7β2nAChR(-/-) mice revealed a metabolic improvement possibly linked to the increase in spontaneous physical activity related to central β2nAChR deficiency.

Published
2014

18. Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36. : Obesity decreases the fat preference

Author

Déborah Ancel, Arnaud Bernard, Michael Chevrot, Isabelle Niot, Marjorie Buttet, Philippe Besnard, Souleymane Abdoul-Azize, Céline Martin, Jean-François Merlin, Naim Akhtar Khan, Hélène Poirier, Patricia Passilly-Degrace, Physiologie de la Nutrition et Toxicologie (NUTox) (U866, Lipides et nutrition, équipe 7) (NUTox), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Burgundy Council and Centre National Interprofessionnel de l'Economie Laitière (CNIEL) (HumanFATaste program), FUI SYMPPA, Physiologie de la Nutrition et Toxicologie (NUTox) (U866, Lipides et nutrition, équipe 7) ( NUTox ), Lipides - Nutrition - Cancer (U866) ( LNC ), and Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA )

Subjects
CD36 Antigens, CD36, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Adipose tissue, MESH : Behavior, Animal, Biochemistry, Calcium in biology, Mice, 0302 clinical medicine, Endocrinology, MESH : Calcium Signaling, MESH: Behavior, Animal, MESH: Obesity, MESH: Animals, Lingual papilla, Research Articles, 2. Zero hunger, 0303 health sciences, MESH : Food Preferences, Behavior, Animal, MESH : Tongue, MESH : Diet, High-Fat, MESH: Tongue, Taste Perception, taste sensitivity, MESH : Antigens, CD36, calcium imaging, Adipose Tissue, Health, MESH: Dietary Fats, MESH : Obesity, Fat taste, MESH: Adipose Tissue, medicine.medical_specialty, Food behavior, 030209 endocrinology & metabolism, MESH : Mice, Inbred C57BL, QD415-436, Biology, Diet, High-Fat, MESH: Calcium Signaling, MESH : Adipose Tissue, Food Preferences, 03 medical and health sciences, Calcium imaging, Tongue, Downregulation and upregulation, MESH: Mice, Inbred C57BL, Internal medicine, MESH : Mice, medicine, Animals, Calcium Signaling, Obesity, Fatty acids, MESH: Food Preferences, MESH: Mice, 030304 developmental biology, Nutrition, long-chain fatty acids, MESH: Antigens, CD36, MESH : Taste Perception, Cell Biology, medicine.disease, Dietary Fats, Mice, Inbred C57BL, MESH: Diet, High-Fat, MESH: Taste Perception, biology.protein, MESH : Animals, Body mass index, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH : Dietary Fats
Abstract

International audience; A relationship between orosensory detection of dietary lipids, regulation of fat intake, and body mass index was recently suggested. However, involved mechanisms are poorly understood. Moreover, whether obesity can directly modulate preference for fatty foods remains unknown. To address this question, exploration of the oral lipid sensing system was undertaken in diet-induced obese (DIO) mice. By using a combination of biochemical, physiological, and behavioral approaches, we found that i) the attraction for lipids is decreased in obese mice, ii) this behavioral change has an orosensory origin, iii) it is reversed in calorie-restricted DIO mice, revealing an inverse correlation between fat preference and adipose tissue size, iv) obesity suppresses the lipid-mediated downregulation of the lipid-sensor CD36 in circumvallate papillae, usually found during the refeeding of lean mice, and v) the CD36-dependent signaling cascade controlling the intracellular calcium levels ([Ca(2+)]i) in taste bud cells is decreased in obese mice. Therefore, obesity alters the lipid-sensing system responsible for the oral perception of dietary lipids. This phenomenon seems to take place through a CD36-mediated mechanism, leading to changes in eating behavior.

Published
2013

19. Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36

Author

Chevrot, Michaël, Bernard, Arnaud, Ancel, Déborah, Buttet, Marjorie, Martin, Céline, Abdoul-Azize, Souleymane, Merlin, Jean-François, Poirier, Hélène, Niot, Isabelle, Khan, Naim Akhtar, Degrace-Passilly, Patricia, Besnard, Philippe, Physiologie de la Nutrition et Toxicologie (NUTox) (U866, Lipides et nutrition, équipe 7) ( NUTox ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Burgundy Council and Centre National Interprofessionnel de l'Economie Laitière (CNIEL) (HumanFATaste program), FUI SYMPPA, Physiologie de la Nutrition et Toxicologie (NUTox) (U866, Lipides et nutrition, équipe 7) (NUTox), Lipides - Nutrition - Cancer (U866) (LNC), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)

Subjects
Food behavior, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Mice, Inbred C57BL, MESH: Calcium Signaling, MESH : Behavior, Animal, MESH : Adipose Tissue, Mice, MESH : Calcium Signaling, MESH: Mice, Inbred C57BL, MESH: Behavior, Animal, MESH : Mice, MESH: Obesity, MESH: Animals, Obesity, Fatty acids, MESH: Food Preferences, MESH: Mice, Nutrition, MESH : Food Preferences, MESH : Tongue, MESH: Antigens, CD36, MESH : Diet, High-Fat, MESH: Tongue, MESH : Taste Perception, MESH: Diet, High-Fat, MESH : Antigens, CD36, MESH: Dietary Fats, Health, MESH: Taste Perception, MESH : Obesity, MESH : Animals, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Fat taste, MESH: Adipose Tissue, MESH : Dietary Fats
Abstract

International audience; A relationship between orosensory detection of dietary lipids, regulation of fat intake, and body mass index was recently suggested. However, involved mechanisms are poorly understood. Moreover, whether obesity can directly modulate preference for fatty foods remains unknown. To address this question, exploration of the oral lipid sensing system was undertaken in diet-induced obese (DIO) mice. By using a combination of biochemical, physiological, and behavioral approaches, we found that i) the attraction for lipids is decreased in obese mice, ii) this behavioral change has an orosensory origin, iii) it is reversed in calorie-restricted DIO mice, revealing an inverse correlation between fat preference and adipose tissue size, iv) obesity suppresses the lipid-mediated downregulation of the lipid-sensor CD36 in circumvallate papillae, usually found during the refeeding of lean mice, and v) the CD36-dependent signaling cascade controlling the intracellular calcium levels ([Ca(2+)]i) in taste bud cells is decreased in obese mice. Therefore, obesity alters the lipid-sensing system responsible for the oral perception of dietary lipids. This phenomenon seems to take place through a CD36-mediated mechanism, leading to changes in eating behavior.

Published
2013

20. Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36

Author

Chevrot, Michaël, Bernard, Arnaud, Ancel, Déborah, Buttet, Marjorie, Martin, Céline, Abdoul-Azize, Souleymane, Merlin, Jean-François, Poirier, Hélène, Niot, Isabelle, Khan, Naim Akhtar, Degrace-Passilly, Patricia, Besnard, Philippe, Bernard, Arnaud, Physiologie de la Nutrition et Toxicologie (NUTox) (U866, Lipides et nutrition, équipe 7) (NUTox), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), and Burgundy Council and Centre National Interprofessionnel de l'Economie Laitière (CNIEL) (HumanFATaste program), FUI SYMPPA

Subjects
Food behavior, MESH: Antigens, CD36, MESH: Tongue, MESH: Calcium Signaling, Mice, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Diet, High-Fat, Health, MESH: Dietary Fats, MESH: Mice, Inbred C57BL, MESH: Taste Perception, MESH: Behavior, Animal, MESH: Obesity, MESH: Animals, Obesity, Fatty acids, MESH: Food Preferences, Fat taste, MESH: Mice, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Adipose Tissue, Nutrition
Abstract

International audience; A relationship between orosensory detection of dietary lipids, regulation of fat intake, and body mass index was recently suggested. However, involved mechanisms are poorly understood. Moreover, whether obesity can directly modulate preference for fatty foods remains unknown. To address this question, exploration of the oral lipid sensing system was undertaken in diet-induced obese (DIO) mice. By using a combination of biochemical, physiological, and behavioral approaches, we found that i) the attraction for lipids is decreased in obese mice, ii) this behavioral change has an orosensory origin, iii) it is reversed in calorie-restricted DIO mice, revealing an inverse correlation between fat preference and adipose tissue size, iv) obesity suppresses the lipid-mediated downregulation of the lipid-sensor CD36 in circumvallate papillae, usually found during the refeeding of lean mice, and v) the CD36-dependent signaling cascade controlling the intracellular calcium levels ([Ca(2+)]i) in taste bud cells is decreased in obese mice. Therefore, obesity alters the lipid-sensing system responsible for the oral perception of dietary lipids. This phenomenon seems to take place through a CD36-mediated mechanism, leading to changes in eating behavior.

Published
2013

21. Deletion of C/EBP homologous protein (Chop) in C57Bl/6 mice dissociates obesity from insulin resistance

Author

Aurélie Waget, Miriam Cnop, Lutgart Overbergh, Decio L. Eizirik, João Paulo Monteiro Carvalho Mori da Cunha, Alessandra K Cardozo, Chantal Mathieu, Michael Maris, E Verdrengh, Conny Gysemans, Tomomi Gotoh, Rémy Burcelin, Laboratory for Experimental Medicine and Endocrinology, Catholic University of Leuven (LEGENDO), Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Experimental Medicine, Université Libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Department of School Health, Faculty of Education & Department of Molecular Genetics, Kumamoto University, Kumamoto, Kumamoto University, Simon, Marie Francoise, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles (ULB)

Subjects
MESH: Inflammation, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, CHOP, MESH: Mice, Knockout, MESH: Insulin-Secreting Cells, Mice, 0302 clinical medicine, Insulin-Secreting Cells, Insulin, MESH: Obesity, MESH: Animals, MESH: Fatty Liver, Mice, Knockout, 0303 health sciences, Sciences bio-médicales et agricoles, MESH: Insulin Resistance, Adipose Tissue, Liver, MESH: Transcription Factor CHOP, medicine.symptom, Beta cell, MESH: Adipose Tissue, medicine.medical_specialty, Inflammation, MESH: Insulin, 03 medical and health sciences, Insulin resistance, Internal medicine, Glucose Intolerance, Internal Medicine, medicine, Animals, Obesity, MESH: Mice, MESH: Glucose Intolerance, 030304 developmental biology, business.industry, Endoplasmic reticulum, CHOP. Endoplasmic reticulum-Inflammation-Obesity. Steatosis-Type 2 diabetes, medicine.disease, Fatty Liver, Endocrinology, Apoptosis, Unfolded protein response, Médecine clinique [biologie clinique], Insulin Resistance, business, Transcription Factor CHOP, 030217 neurology & neurosurgery, MESH: Liver
Abstract

AIMS/HYPOTHESIS: Endoplasmic reticulum (ER) stress has been implicated in the development of type 2 diabetes, via effects on obesity, insulin resistance and pancreatic beta cell health. C/EBP homologous protein (CHOP) is induced by ER stress and has a central role in apoptotic execution pathways triggered by ER stress. The aim of this study was to characterise the role of CHOP in obesity and insulin resistance. METHODS: Metabolic studies were performed in Chop ( -/- ) and wild-type C57Bl/6 mice, and included euglycaemic-hyperinsulinaemic clamps and indirect calorimetry. The inflammatory state of liver and adipose tissue was determined by quantitative RT-PCR, immunohistology and macrophage cultures. Viability and absence of ER stress in islets of Langerhans was determined by electron microscopy, islet culture and quantitative RT-PCR. RESULTS: Systemic deletion of Chop induced abdominal obesity and hepatic steatosis. Despite marked obesity, Chop ( -/- ) mice had preserved normal glucose tolerance and insulin sensitivity. This discrepancy was accompanied by lower levels of pro-inflammatory cytokines and less infiltration of immune cells into fat and liver. CONCLUSIONS/INTERPRETATION: These observations suggest that insulin resistance is not induced by fat accumulation per se, but rather by the inflammation induced by ectopic fat. CHOP may play a key role in the crosstalk between excessive fat deposition and induction of inflammation-mediated insulin resistance., JOURNAL ARTICLE, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2012

22. Catecholamine and insulin control of lipolysis in subcutaneous adipose tissue during long-term diet-induced weight loss in obese women

Author

Jan Polak, Isabelle de Glisezinski, Marie Adeline Marques, Katrien Koppo, Dominique Langin, Michel Berlan, Michaela Siklova-Vitkova, Vladimir Stich, Jens Bülow, Johan Van de Voorde, Eva Klimcakova, Department of Sports Medicine, Charles University [Prague] (CU), Department of Pharmacology, Universiteit Gent = Ghent University [Belgium] (UGENT), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Physiology, Bispebjerg Hospital-Universiy of Copenhagen, Service de biochimie clinique, CHU Toulouse [Toulouse], Service de médecine du sport, Simon, Marie Francoise, Universiteit Gent = Ghent University (UGENT), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Médecine du Sport [CHU Toulouse], Département Chirurgie Orthopédique et traumatologique [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
Physiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Adipose tissue, Adrenergic, MESH: Glucose Clamp Technique, 0302 clinical medicine, Catecholamines, Weight loss, Medicine, Insulin, MESH: Obesity, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Diet, Reducing, 0303 health sciences, Glucose clamp technique, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Insulin Resistance, Epinephrine, Adipose Tissue, Female, medicine.symptom, MESH: Adipose Tissue, medicine.drug, Adult, medicine.medical_specialty, Diet, Reducing, Lipolysis, Calorie restriction, 030209 endocrinology & metabolism, MESH: Insulin, 03 medical and health sciences, MESH: Weight Loss, Physiology (medical), Internal medicine, Weight Loss, MESH: Catecholamines, Humans, MESH: Lipolysis, Obesity, 030304 developmental biology, Caloric Restriction, MESH: Caloric Restriction, MESH: Humans, business.industry, MESH: Adult, Endocrinology, Glucose Clamp Technique, Insulin Resistance, business, MESH: Female
Abstract

The aim of this study was to investigate the evolution of the adrenergic and insulin-mediated regulation of lipolysis during different phases of a 6-mo dietary intervention. Eight obese women underwent a 6-mo dietary intervention consisting of a 1-mo very low-calorie diet (VLCD) followed by a 2-mo low-calorie diet (LCD) and 3-mo weight maintenance (WM) diet. At each phase of the dietary intervention, microdialysis of subcutaneous adipose tissue (SCAT) was performed at rest and during a 3-h hyperinsulinemic euglycemic clamp. Responses of dialysate glycerol concentration (DGC) were determined at baseline and during local perfusions with adrenaline or adrenaline and phentolamine before and during the last 30 min of the clamp. Dietary intervention induced a body weight reduction and an improved insulin sensitivity. DGC progressively decreased during the clamp, and this decrease was similar during the different phases of the diet. The adrenaline-induced increase in DGC was higher at VLCD and LCD compared with baseline condition and returned to prediet levels at WM. In the probe with adrenaline and phentolamine, the increase in DGC was higher than that in the adrenaline probe at baseline and WM, but it was not different at VLCD and LCD. The results suggest that the responsiveness of SCAT to adrenaline-stimulated lipolysis increases during the calorie-restricted phases due to a reduction of the α2-adrenoceptor-mediated antilipolytic action of adrenaline. At WM, adrenaline-stimulated lipolysis returned to the prediet levels. Furthermore, no direct relationship between insulin sensitivity and the diet-induced changes in the regulation of lipolysis was found.

Published
2012

23. Activation of protein kinase A and exchange protein directly activated by cAMP promotes adipocyte differentiation of human mesenchymal stem cells

Author

Bingbing Jia, Reidun K. Kopperud, Gérard Ailhaud, Nathalie Techer, Karsten Kristiansen, Ez-Zoubir Amri, Jinfu Wang, Rasmus Koefoed Petersen, Stein Ove Døskeland, Lise Madsen, Tao Ma, Dept. Biochemistry and Molecular Biology, Odense, University of Southern Denmark (SDU), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Biochemistry and Molecular Biology, Department of Biology [Copenhagen], Faculty of Science [Copenhagen], and University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)

Subjects
MESH: Signal Transduction, IBMX, Cellular differentiation, lcsh:Medicine, MESH: Thiazolidinediones, Biochemistry, Dexamethasone, chemistry.chemical_compound, Mice, 0302 clinical medicine, Adipocyte, 1-Methyl-3-isobutylxanthine, Molecular Cell Biology, Adipocytes, Cyclic AMP, MESH: Guanine Nucleotide Exchange Factors, MESH: Obesity, Guanine Nucleotide Exchange Factors, Insulin, MESH: Animals, lcsh:Science, [SDV.BDD]Life Sciences [q-bio]/Development Biology, MESH: Cyclic AMP, 0303 health sciences, Multidisciplinary, Stem Cells, MESH: 1-Methyl-3-isobutylxanthine, Cell Differentiation, MESH: Gene Expression Regulation, Lipids, Signaling Cascades, Cell biology, Adipose Tissue, Adipogenesis, MESH: Dexamethasone, 030220 oncology & carcinogenesis, Signal transduction, MESH: Adipose Tissue, Research Article, Signal Transduction, MESH: Cell Differentiation, medicine.medical_specialty, MESH: Insulin, MESH: Cyclic AMP-Dependent Protein Kinases, MESH: Epoprostenol, Biology, Cell Line, Rosiglitazone, MESH: Gene Expression Profiling, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, Obesity, Protein kinase A, MESH: Mice, MESH: Adipocytes, 030304 developmental biology, MESH: Humans, Gene Expression Profiling, Mesenchymal stem cell, lcsh:R, Mesenchymal Stem Cells, Cyclic AMP-Dependent Protein Kinases, Epoprostenol, MESH: Cell Line, MESH: Mesenchymal Stem Cells, Endocrinology, chemistry, Gene Expression Regulation, Cell culture, Thiazolidinediones, lcsh:Q, Developmental Biology
Abstract

Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence of the strong adipogenic inducers insulin, dexamethasone, and rosiglitazone, thereby clearly distinguishing the hMADS cells from murine preadipocytes cell lines, where rosiglitazone together with dexamethasone and insulin strongly promotes adipocyte differentiation. We further show that prostaglandin I(2) (PGI(2)) may fully substitute for the cAMP-elevating agent isobutylmethylxanthine (IBMX). Moreover, selective activation of Epac-dependent signaling promoted adipocyte differentiation when the Rho-associated kinase (ROCK) was inhibited. Unlike the case for murine preadipocytes cell lines, long-chain fatty acids, like arachidonic acid, did not promote adipocyte differentiation of hMADS cells in the absence of a PPARγ agonist. However, prolonged treatment with the synthetic PPARδ agonist L165041 promoted adipocyte differentiation of hMADS cells in the presence of IBMX. Taken together our results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells.

Published
2012

24. Multiple effects of a short-term dexamethasone treatment in human skeletal muscle and adipose tissue

Author

Flora Picard, Carine Valle, P. Barbe, Jason S. Iacovoni, Nathalie Viguerie, Balbine Roussel, Wim H. M. Saris, Gabby B. Hul, Dominique Langin, Simon, Marie Francoise, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Department of Human Biology, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Humane Biologie, RS: NUTRIM - R1 - Metabolic Syndrome, Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]

Subjects
Male, MESH: Serum Amyloid A Protein, Physiology, Adipose tissue, Dexamethasone, ACTIVATION, 0302 clinical medicine, Mineralocorticoid receptor, Longitudinal Studies, MESH: Longitudinal Studies, GENE-EXPRESSION, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, MESH: Muscle, Skeletal, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, C-Reactive Protein, medicine.anatomical_structure, Adipose Tissue, MESH: Dexamethasone, medicine.symptom, Glucocorticoid, MESH: Adipose Tissue, medicine.drug, Adult, medicine.medical_specialty, Adipose tissue macrophages, 030209 endocrinology & metabolism, Inflammation, Biology, METABOLISM, 03 medical and health sciences, Downregulation and upregulation, MICROARRAY, INFLAMMATION, Internal medicine, MESH: C-Reactive Protein, Genetics, medicine, gene expression profiling, Humans, GLUCOCORTICOIDS, Muscle, Skeletal, 030304 developmental biology, Serum Amyloid A Protein, MESH: Humans, Skeletal muscle, 3T3-L1 ADIPOCYTES, MESH: Adult, INSULIN-RESISTANT MICE, MESH: Male, Endocrinology, healthy volunteers, SERUM-AMYLOID-A, CELLS, glucocorticoid, MESH: Glucocorticoids
Abstract

Viguerie N, Picard F, Hul G, Roussel B, Barbe P, Iacovoni JS, Valle C, Langin D, Saris WHM. Multiple effects of a short-term dexamethasone treatment in human skeletal muscle and adipose tissue. Physiol Genomics 44: 141-151, 2012. First published November 22, 2011; doi:10.1152/physiolgenomics.00032.2011.-Glucocorticoids are frequently prescribed drugs with important side-effects such as glucose intolerance and tissue remodeling. The goal was to explore the molecular basis of the response of skeletal muscle and adipose tissue during a short-term dexamethasone treatment to better understand the induction of side-effects of glucocorticoids on these metabolic tissues. Fifteen healthy male subjects were assigned to a 4-day treatment with dexamethasone at 4 mg/day. The primary outcome measures were changes in gene expression profiling of subcutaneous skeletal muscle and adipose tissue. Urinary cortisol, plasma, and metabolic biochemistry were also assessed. In both tissues the prominent observation was a response to stress and increased inflammatory responses. An upregulation of the serum amyloid A was detected in skeletal muscle, adipose tissue, and plasma, whereas circulating levels of C reactive protein, another acute phase protein, decreased along with a worsened insulin sensitivity index. As tissue-specific features, tissue remodeling was shown in skeletal muscle while the adipose tissue exhibited a decreased energy metabolism. Several limitations might be raised due to the small number of subjects investigated: a possible cross talk with the mineralocorticoid receptor, and a single time point may not identify regulations occurring during longitudinal treatment. In line with the known physiological effect of glucocorticoids the early modulation of stress response genes was observed. An unexpected feature was the upregulation of the inflammatory and immune pathways. The identification of novel impact on two glucocorticoid target tissues provides a molecular basis for the design of more specific glucocorticoids devoid of adverse effects.

Published
2012

25. An evaluation of the effects of Lactobacillus ingluviei on body weight, the intestinal microbiome and metabolism in mice

Author

Marie-Christine Alessi, Adil El Filali, Didier Raoult, Emmanouil Angelakis, Delphine Bastelica, Anne Dutour, Jean-Louis Mege, Amira Ben Amara, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, animal diseases, Adipose tissue, Gut flora, Weight Gain, Mice, Lactobacillus, MESH: Obesity, MESH: Animals, Intestinal Mucosa, 2. Zero hunger, Mice, Inbred BALB C, 0303 health sciences, Leptin, food and beverages, CYP2E1, 3. Good health, Intestines, Infectious Diseases, Adipose Tissue, Liver, MESH: Weight Gain, MESH: Intestinal Mucosa, Female, medicine.symptom, Sterol Regulatory Element Binding Protein 1, MESH: Adipose Tissue, MESH: Intestines, medicine.medical_specialty, animal structures, Firmicutes, education, MESH: Mice, Inbred BALB C, Biology, Microbiology, 03 medical and health sciences, MESH: Sterol Regulatory Element Binding Protein 1, Internal medicine, medicine, Animals, Obesity, MESH: Mice, 030304 developmental biology, Adiponectin, 030306 microbiology, Probiotics, Body Weight, fungi, MESH: Metagenome, biology.organism_classification, MESH: Male, MESH: Body Weight, PPAR gamma, Endocrinology, MESH: PPAR gamma, Metagenome, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Weight gain, MESH: Female, MESH: Lactobacillus, MESH: Probiotics, MESH: Liver
Abstract

Background Food can modify the intestinal flora, and Lactobacillus ingluviei has been shown to cause weight gain in chicks and ducks but not in mammals. Methodology Female BALB/c mice were divided into a control and two experimental groups and were inoculated either once or twice with L. ingluviei or with PBS. Faecal samples were collected and tested using qPCR in order to detect and quantify Lactobacillus spp., Bacteroidetes spp. and Firmicutes spp. Gene expression was examined in liver and adipose tissue by microarray and qPCR. Metabolic indicators in the plasma were also measured. Results Mice that were inoculated with 4 × 1010 L. ingluviei presented a significant increase in weight gain and liver weight and significant increases in Lactobacillus spp. and Firmicutes DNA copy numbers in their faeces. The mRNA levels of fatty acyl synthase (Fas), sterol regulatory element binding factor 1 (Srebp1c), tumour necrosis factor alpha (Tnf), cytochrome P450 2E1 (Cyp2e1), 3-phosphoinositide-dependent protein kinase-1 (Pdpk1), acyl-Coenzyme A dehydrogenase 11 (Acad11), ATP-binding cassette sub family member G (ABCG2) and DEAD box polypeptide 25 (Ddx25) were significantly elevated in the liver tissues of animals in the experimental group. In gonadal adipose tissue, the expression levels of leptin, peroxisome proliferator-activated receptor γ (Pparg) and Srebp1c were significantly higher in animals from the experimental group, whereas the expression of adiponectin was significantly lower in these animals. Conclusions The inoculation of L. ingluviei in mice resulted in alterations in the intestinal flora, increased weight gain and liver enlargement, accelerated metabolism and increased inflammation.

Published
2012

26. Downregulation of the tumour suppressor p16INK4A contributes to the polarisation of human macrophages toward an adipose tissue macrophage (ATM)-like phenotype

Author

Céline Cudejko, Réjane Paumelle, Lucía Fuentes, Sarah Anissa Hannou, Thérèse Hèrvée Mayi, François Pattou, Giulia Chinetti-Gbaguidi, Elena Rigamonti, Kristiaan Wouters, Bart Staels, Bruno Derudas, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de chirurgie générale et endocrinienne, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Therapie Cellulaire du Diabete, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, This work was supported by the EU FP6 grant (EIF 040851 to L. Fuentes), EU FP7 grants (PIEFGA- 2009-23522 to K. Wouters and grant no. 201608 to T. H. Mayi), an EFSD/GlaxoSmithKline Research Grant 2009 (K. Wouters and B. Staels), the Spanish Government MEC (Ministerio de Educación y Ciencia to L. Fuentes) and the Fondation pour la Recherche Médicale (DCV20070409276 to B. Staels), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Derudas, Marie-Hélène

Subjects
Male, Endocrinology, Diabetes and Metabolism, Adipose tissue, MESH: NF-kappa B, MESH: Down-Regulation, law.invention, 0302 clinical medicine, law, MESH: RNA, Small Interfering, MESH: Obesity, MESH: Gene Silencing, RNA, Small Interfering, 0303 health sciences, Adipose tissue macrophages, NF-kappa B, Cell Polarity, Type 2 diabetes, MESH: Toll-Like Receptor 4, Phenotype, Plaque, Atherosclerotic, Adipose Tissue, 030220 oncology & carcinogenesis, MESH: Cyclin-Dependent Kinase Inhibitor p16, Female, medicine.symptom, MESH: Cell Polarity, MESH: Adipose Tissue, MESH: Diabetes Mellitus, Type 2, Down-Regulation, Inflammation, Biology, Senescence, Article, 03 medical and health sciences, CDKN2A, Downregulation and upregulation, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Internal Medicine, medicine, Humans, Gene silencing, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene Silencing, Obesity, MESH: Plaque, Atherosclerotic, neoplasms, Cyclin-Dependent Kinase Inhibitor p16, 030304 developmental biology, MESH: Humans, Macrophages, MESH: Macrophages, Macrophage polarisation, NFKB1, MESH: Male, Toll-Like Receptor 4, Diabetes Mellitus, Type 2, Immunology, Cancer research, Suppressor, MESH: Female
Abstract

Human adipose tissue macrophages (ATMs) display an alternatively activated (M2) phenotype, but are still able to produce excessive inflammatory mediators. However, the processes driving this particular ATM phenotype are not understood. Genome-wide association studies associated the CDKN2A locus, encoding the tumour suppressor p16(INK4A), with the development of type 2 diabetes. In the present study, p16(INK4A) levels in human ATMs and the role of p16(INK4A) in acquiring the ATM phenotype were assessed.Gene expression of p16 ( INK4A ) in ATMs was analysed and compared with that in monocyte-derived macrophages (MDMs) from obese patients or with macrophages from human atherosclerotic plaques (AMs). Additionally, p16(INK4A) levels were studied during macrophage differentiation and polarisation of monocytes isolated from healthy donors. The role of p16(INK4A) in MDMs from healthy donors was investigated by small interfering (si)RNA-mediated silencing or adenovirus-mediated overproduction of p16(INK4A).Compared with MDMs and AMs, ATMs from obese patients expressed lower levels of p16 ( INK4A ). In vitro, IL-4-induced M2 polarisation resulted in lower p16(INK4A) protein levels after differentiation of monocytes from healthy donors in macrophages. Silencing of p16(INK4A) in MDMs mediated by siRNA increased the expression of M2 marker genes and enhanced the response to lipopolysaccharide (LPS), to give a phenotype resembling that of ATM. By contrast, adenovirus-mediated overproduction of p16(INK4A) in MDMs diminished M2 marker gene expression and the response to LPS. Western blot analysis revealed that p16(INK4A) overproduction inhibits LPS- and palmitate-induced Toll-like receptor 4 (TLR4)-nuclear factor of κ light polypeptide gene enhancer in B cells (NF-κB) signalling.These results show that p16(INK4A) inhibits the acquisition of the ATM phenotype. The age-related increase in p16(INK4A) level may thus influence normal ATM function and contribute to type 2 diabetes risk.

Published
2011

27. On the Futility of Screening for Genes That Make You Fat

Author

Terho Lehtimäki, Emily Sonestedt, Göran Hallmans, Andy R Ness, Simin Liu, Tuija Tammelin, John J. Nolan, Massimo Mangino, Nicholas J. Timpson, George Dedoussis, Aline Meirhaeghe, Lu Qi, Pål R. Njølstad, Ruth J. F. Loos, Mustafa Atalay, Mao Fu, Natalia V. Rivera, Marju Orho-Melander, Thorkild I. A. Sørensen, Philippe Froguel, André G. Uitterlinden, Torben Hansen, Debbie A Lawlor, M. Carola Zillikens, Tapani Rönnemaa, Vilmundur Gudnason, Esther Zimmermann, Claes Ohlsson, Cornelia M. van Duijn, Paul M. Ridker, Marjo-Riitta Järvelin, Samia Mora, María Teresa Martínez Larrad, Alena Stančáková, Thomas Illig, Zoltán Kutalik, Sven Bergmann, Jonatan R. Ruiz, Luigi Palla, Kathleen A. Jablonski, Günther Silbernagel, Ulla Sovio, Soren Snitker, Karina Meidtner, Bo Isomaa, Stephen J. Sharp, Jana V. van Vliet-Ostaptchouk, Louis Pérusse, Mika Kähönen, Daniel I. Chasman, Najaf Amin, Johanna Kuusisto, Toshiko Tanaka, Ingrid B. Borecki, John-Olov Jansson, Christine Cavalcanti-Proença, N. Charlotte Onland-Moret, Kay-Tee Khaw, Camilla H. Sandholt, Ulf Ekelund, Luigi Ferrucci, Mark Walker, Yiqing Song, Jose C. Florez, Oluf Pedersen, Leif Groop, Ying Wu, Soren Brage, Tuomas O. Kilpeläinen, Anders Grøntved, Frida Renström, Meena Kumari, Stéphane Cauchi, Michael Boehnke, Tamara B. Harris, Christine S. Autenrieth, Jeffery Metter, Beverley Balkau, Dmitry Shungin, Karen L. Mohlke, Markku Laakso, Matti Uusitupa, Nicholas J. Wareham, Andreas Fritsche, Jaakko Tuomilehto, Albert Hofman, Shah Ebrahim, Mary F. Feitosa, Melissa E. Garcia, Stefan Johansson, Tim D. Spector, Paul W. Franks, E. Shyong Tai, Frank B. Hu, Jonathan T. Tan, Maarit Hakanen, Heiner Boeing, Manuel Serrano Ríos, Olli T. Raitakari, Michael Marmot, Meian He, Jennifer L. Bragg-Gresham, Claude Bouchard, Tariq Ahmad, Ellen W. Demerath, Keri L. Monda, Robert A. Scott, Marika Kaakinen, Chris Power, Stefania Bandinelli, Christina Holzapfel, Timo A. Lakka, Heather M. Stringham, Stavroula Kanoni, Elina Hyppönen, Pamela L. Lutsey, Internal Medicine, Medical Microbiology & Infectious Diseases, Epidemiology, Urology, Institute of Metabolic Science, MRC, Departments of Epidemiology and Nutrition, Harvard School of Public Health, Department of Clinical Sciences, Lund University Diabetes Centre-Lund University [Lund], Division of Epidemiology and Community Health, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Division of Cardiology, Duke University Medical Center, Brigham and Women's Hospital [Boston], Institute of Health Sciences and Biocenter Oulu, University of Oulu, Hagedorn Research Institute, Else Kroener Fresenius Centre - Zentralinstitut für Ernährungs und Lebensmittelfors (ZIEL), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Department of Population Health Sciences, University of Wisconsin-Madison, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Centre for Paediatric Epidemiology and Biostatistics, University College of London [London] (UCL), MRC Centre for Epidemiology of Child Health, UCL Institute of Child Health, Institut de biologie de Lille - UMS 3702 (IBL), Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Genetics, Université de Lausanne (UNIL), Department of Epidemiology and Public Health, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Department of Epidemiology, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association-Leibniz Association, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National University of Singapore (NUS)-Yong Loo Lin School of Medicine, King‘s College London, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, Division of Preventive Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Department of Internal Medicine, Erasmus University Medical Center [Rotterdam] (Erasmus MC), The Biostatistics Center, The George Washington University (GW), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Mental Health Sciences Unit, Department of Clinical Medicine, University of Bergen (UiB), Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Genetics, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Complex Genetics Section, University Medical Center [Utrecht], Julius Center for Health Sciences and Primary Care, Institute of Preventive Medicine, Copenhagen University Hospital, Department of Biomedical Sciences [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Genetic Epidemiology Unit, Medstar Research Institute, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Department of Nutrition-Dietetics, Harokopio University of Athens, Division of Statistical Genomics, Washington University School of Medicine, University of Maryland School of Medicine, University of Maryland System, Unit for Preventive Nutrition, Karolinska Institutet [Stockholm], Department of Physical Education and Sport, University of Granada [Granada], Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Hospital Clínico San Carlos, Department of Physiology, University of Eastern Finland-Institute of Biomedicine, The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Institute of Sport Science and Clinical Biomechanics, University of Southern Denmark (SDU), Department of Public Health and Clinical Medicine/Nutritional Research, Umeå University, Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU)-Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Clinical Physiology, University of Tampere [Finland]-Tampere University Hospital, Steno Diabetes Centre, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health Sciences, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Department of Medical Statistics, London School of Hygiene and Tropical Medicine (LSHTM), LIKES Research Center for Sport and Health Sciences, Finnish Institute of Occupational Health, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University (LSU)-Louisiana State University (LSU), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Division of Endocrinology, Diabetes and Nutrition, University of Maryland System-University of Maryland System, Institute of Cell and Molecular Biosciences, Newcastle University [Newcastle], Centre for Bone and Arthritis Research, Institute of Medicine-University of Gothenburg (GU), Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Centre for Medical Systems Biology, Faculty of Epidemiology and Population Health [London], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland [Reykjavik], Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Department of Clinical Chemistry, Turku University Hospital (TYKS), Folkhälsan Research Centre, Department of Pediatrics, Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB), Center for Human Genetic Research and Diabetes Research Center, Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Program for Medical and Population Genetics, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Center for Metabolic Disease Prevention, University of California [Los Angeles] (UCLA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, School of Oral and Dental Sciences, University of Bristol [Bristol], National University of Singapore (NUS), Department of Genomics of Common Disease, Imperial College London, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Department of Epidemiology and Biostatistics, Department of Life Course and Services, National Institute for Health and Welfare [Helsinki], Autard, Delphine, Lund University [Lund], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Universidad de Granada = University of Granada (UGR), University of Gothenburg (GU)-Institute of Medicine, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), Medical Research Council (MRC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Brage, Soren [0000-0002-1265-7355], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Hjelt Institute (-2014), Harvard University-Massachusetts Institute of Technology (MIT)-Harvard University-Massachusetts Institute of Technology (MIT), Kilpeläinen, Tuomas O, Qi, Lu, Brage, Soren, Sharp, Stephen J, Hypponen, Elina, and Loos, Ruth JF

Subjects
Male, Heredity, endocrine system diseases, Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714 [VDP], Epidemiology, Social and Behavioral Sciences, no keywords, MESH: Genotype, 0302 clinical medicine, MESH: Child, GENETIC-VARIANTS, MESH: Proteins, 10. No inequality, Child, 0303 health sciences, Anthropometry, MESH: Polymorphism, Single Nucleotide, General Medicine, 11 Medical And Health Sciences, Genomics, MESH: Motor Activity, Adipose Tissue, Perspective, Medicine, Public Health, WAIST CIRCUMFERENCE, MESH: Adipose Tissue, medicine.medical_specialty, Genotype, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Endocrinology and Diabetes, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genomic Medicine, Genetics, Humans, Genetic Testing, Gene Prediction, Biology, Adipose Tissue/metabolism, Adolescent, Adult, Aged, Female, Genetic Predisposition to Disease, Motor Activity, Obesity/genetics, Obesity/metabolism, Polymorphism, Single Nucleotide, Proteins/genetics, Risk Factors, MESH: Adolescent, Science & Technology, MESH: Humans, Computational Biology, nutritional and metabolic diseases, Proteins, MESH: Adult, Odds ratio, medicine.disease, Obesity, RS9939609 POLYMORPHISM, Endocrinology, Anthropology, Physiological Processes, Body mass index, MESH: Female, Population Genetics, obesity, Genetic Screens, Anatomy and Physiology, FTO gene, IDENTICAL-TWINS, MESH: Risk Factors, MESH: Obesity, adolescents, 030212 general & internal medicine, MESH: Aged, MESH: Genetic Predisposition to Disease, 3142 Public health care science, environmental and occupational health, ENVIRONMENT INTERACTION, Genetic Epidemiology, childhood obesity, Life Sciences & Biomedicine, Research Article, Clinical Research Design, UNITED-STATES, WEIGHT-LOSS, Childhood obesity, body weight, Medicine, General & Internal, Genome Analysis Tools, Internal medicine, General & Internal Medicine, medicine, Allele, Sports and Exercise Medicine, Genetic Association Studies, 030304 developmental biology, Nutrition, Clinical Genetics, Population Biology, business.industry, Human Genetics, MESH: Male, COMMON VARIANT, meta-analysis, Minor allele frequency, BODY-MASS INDEX, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Genetics of Disease, Genetic Polymorphism, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Meta-Analyses, business, Energy Metabolism, genetic predisposition, DIABETES PREVENTION
Abstract

Ruth Loos and colleagues report findings from a meta-analysis of multiple studies examining the extent to which physical activity attenuates effects of a specific gene variant, FTO, on obesity in adults and children. They report a fairly substantial attenuation by physical activity on the effects of this genetic variant on the risk of obesity in adults., Background The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings All studies identified to have data on the FTO rs9939609 variant (or any proxy [r 2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A−) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20–1.26), but PA attenuated this effect (p interaction = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19–1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24–1.36). No such interaction was found in children and adolescents. Conclusions The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity. Please see later in the article for the Editors' Summary, Editors’ Summary Background Two in three Americans are overweight, of whom half are obese, and the trend towards increasing obesity is now seen across developed and developing countries. There has long been interest in understanding the impact of genes and environment when it comes to apportioning responsibility for obesity. Carrying a change in the FTO gene is common (found in three-quarters of Europeans and North Americans) and is associated with a 20%–30% increased risk of obesity. Some overweight or obese individuals may feel that the dice are loaded and there is little point in fighting the fat; it has been reported that those made aware of their genetic susceptibility to obesity may still choose a poor diet. A similar fatalism may occur when overweight and obese people consider physical activity. But disentangling the influence of physical activity on those genetically susceptible to obesity from other factors that might impact weight is not straightforward, as it requires large sample sizes, could be subject to publication bias, and may rely on less than ideal self-reporting methods. Why Was This Study Done? The public health ramifications of understanding the interaction between genetic susceptibility to obesity and physical activity are considerable. Tackling the rising prevalence of obesity will inevitably include interventions principally aimed at changing dietary intake and/or increasing physical activity, but the evidence for these with regards to those genetically susceptible has been lacking to date. The authors of this paper set out to explore the interaction between the commonest genetic susceptibility trait and physical activity using a rigorous meta-analysis of a large number of studies. What Did the Researchers Do and Find? The authors were concerned that a meta-analysis of published studies would be limited both by the data available to them and by possible bias. Instead of this more widely used approach, they took the literature search as their starting point, identified other studies through their collaborators’ network, and then undertook a meta-analysis of all available studies using a new and standardized analysis plan. This entailed an extremely large number of authors mining their data afresh to extract the relevant data points to enable such a meta-analysis. Physical activity was identified in the original studies in many different ways, including by self-report or by using an external measure of activity or heart rate. In order to perform the meta-analysis, participants were labeled as physically active or inactive in each study. For studies that had used a continuous scale, the authors decided that the bottom 20% of the participants were inactive (10% for children and adolescents). Using data from over 218,000 adults, the authors found that carrying a copy of the susceptibility gene increased the odds of obesity by 1.23-fold. But the size of this influence was 27% less in the genetically susceptible adults who were physically active (1.22-fold) compared to those who were physically inactive (1.30-fold). In a smaller study of about 19,000 children, no such effect of physical activity was seen. What Do these Findings Mean? This study demonstrates that people who carry the susceptibility gene for obesity can benefit from physical activity. This should inform health care professionals and the wider public that the view of genetically determined obesity not being amenable to exercise is incorrect and should be challenged. Dissemination, implementation, and ensuring uptake of effective physical activity programs remains a challenge and deserves further consideration. That the researchers treated “physically active” as a yes/no category, and how they categorized individuals, could be criticized, but this was done for pragmatic reasons, as a variety of means of assessing physical activity were used across the studies. It is unlikely that the findings would have changed if the authors had used a different method of defining physically active. Most of the studies included in the meta-analysis looked at one time point only; information about the influence of physical activity on weight changes over time in genetically susceptible individuals is only beginning to emerge. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001116. This study is further discussed in a PLoS Medicine Perspective by Lennert Veerman The US Centers for Disease Control and Prevention provides obesity-related statistics, details of prevention programs, and an overview on public health strategy in the United States A more worldwide view is given by the World Health Organization The UK National Health Service website gives information on physical activity guidelines for different age groups, while similar information can also be found from US sources

Published
2011

28. Macrophage polarization in metabolic disorders: functions and regulation

Author

Bart Staels, Giulia Chinetti-Gbaguidi, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Grants from the Région Nord-Pas de Calais/FEDER (CPER N. 1449), COST actions BM0602 and BM0904, the Agence Nationale de la Recherche (AlMHA project), the transatlantic Leducq HDL Network, the Fondation Coeur et Artères and the European Community's 7th Framework Programme (FP7/2007-2013, grant agreement n° 201608) are acknowledged., and Derudas, Marie-Hélène

Subjects
Vascular wall, MESH: Inflammation, Pathology, medicine.medical_specialty, obesity, Endocrinology, Diabetes and Metabolism, Adipose tissue macrophages, Macrophage polarization, Adipose tissue, nuclear receptors, MESH: Metabolic Diseases, 030204 cardiovascular system & hematology, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Metabolic Diseases, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, medicine, Animals, Humans, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, Inflammation, 0303 health sciences, Nutrition and Dietetics, MESH: Humans, MESH: Macrophages, Cell Biology, 3. Good health, macrophages, Adipose Tissue, atherosclerosis, Cardiology and Cardiovascular Medicine, MESH: Adipose Tissue
Abstract

International audience; PURPOSE OF REVIEW: To discuss recent findings on the role and regulation of macrophage polarization in obesity and atherosclerosis. RECENT FINDINGS: Macrophages infiltrate the vascular wall during atherosclerosis and adipose tissue during obesity. At least two distinct subpopulations with different functions, the classically (M1) and the alternatively (M2) activated macrophages, have been found in these tissues. Reciprocal skewing of macrophage polarization between the M1 and M2 states is a process modulated by diet, humoral and transcription factors, such as the nuclear receptor peroxisome proliferator-activated receptor gamma. SUMMARY: Recent literature highlights the importance not only of the number of infiltrated macrophages, but also their activation in the maintenance of the inflammation state. Identifying mechanisms and molecules able to modify the balance between M1 and M2 represents a promising field of research.

Published
2011

29. Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat

Author

Pauline Decaunes, Balbine Roussel, Jean-José Maoret, Marion Combes, Michaela Siklova-Vitkova, Nathalie Viguerie, Anne Bouloumié, T Vedral, Zuzana Kovacova, Jindra Hejnova, Dominique Langin, Virginie Bourlier, Michaela Kovacikova, Vladimir Stich, Eva Klimcakova, Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of surgery, University Hospital Kralovské Vinohrady, and Simon, Marie Francoise

Subjects
Macrophage, Endocrinology, Diabetes and Metabolism, Adipose tissue, Overweight, 0302 clinical medicine, MESH: Metabolic Syndrome X, Gene expression, MESH: Obesity, Visceral fat, Cells, Cultured, 2. Zero hunger, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Middle Aged, Metabolic syndrome, Real-time polymerase chain reaction, Adipose Tissue, MESH: Young Adult, Female, medicine.symptom, MESH: Adipose Tissue, MESH: Cells, Cultured, Adult, medicine.medical_specialty, 030209 endocrinology & metabolism, Intra-Abdominal Fat, Biology, Young Adult, 03 medical and health sciences, Insulin resistance, MESH: Subcutaneous Fat, Internal medicine, Diabetes mellitus, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Internal Medicine, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, MESH: Overweight, MESH: Intra-Abdominal Fat, Aged, 030304 developmental biology, Inflammation, MESH: Humans, Macrophages, Subcutaneous fat, nutritional and metabolic diseases, MESH: Macrophages, MESH: Adult, medicine.disease, Human adipose tissue, Endocrinology, MESH: Female
Abstract

International audience; AIMS/HYPOTHESIS: Our goal was to identify a set of human adipose tissue macrophage (ATM)-specific markers and investigate whether their gene expression in subcutaneous adipose tissue (SAT) as well as in visceral adipose tissue (VAT) is related to obesity and to the occurrence of the metabolic syndrome. METHODS: ATM-specific markers were identified by DNA microarray analysis of adipose tissue cell types isolated from SAT of lean and obese individuals. We then analysed gene expression of these markers by reverse transcription quantitative PCR in paired samples of SAT and VAT from 53 women stratified into four groups (lean, overweight, obese and obese with the metabolic syndrome). Anthropometric measurements, euglycaemic-hyperinsulinaemic clamp, blood analysis and computed tomography scans were performed. RESULTS: A panel of 24 genes was selected as ATM-specific markers based on overexpression in ATM compared with other adipose tissue cell types. In SAT and VAT, gene expression of ATM markers was lowest in lean and highest in the metabolic syndrome group. mRNA levels in the two fat depots were negatively correlated with glucose disposal rate and positively associated with indices of adiposity and the metabolic syndrome. CONCLUSIONS/INTERPRETATION: In humans, expression of ATM-specific genes increases with the degree of adiposity and correlates with markers of insulin resistance and the metabolic syndrome to a similar degree in SAT and in VAT.

Published
2011

30. Contribution of IL-17-producing {gamma}{delta} T cells to the efficacy of anticancer chemotherapy

Author

Laurent Boucontet, Laetitia Aymeric, Noelia Casares, Yuting Ma, Guido Kroemer, Nathalie Chaput, Nicolas Ibrahim, Laurence Zitvogel, Clara Locher, Goro Matsuzaki, Bernard Ryffel, Lionel Apetoh, Juan José Lasarte, François Ghiringhelli, Kamel Benlagha, Antoine Tesniere, Julie Déchanet-Merville, Stephen R. Mattarollo, Mark J. Smyth, Pablo Pereira, Nicolas F. Delahaye, Koichi Ikuta, Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Ecole doctorale de cancérologie, Université Paris-Sud - Paris 11 ( UP11 ), Cancer immunology program, Peter MacCallum Cancer Centre, Développement des Lymphocytes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Division of Hepatology and Gene Therapy ( CIMA ), Center for Applied Medical Research [Plamplona] ( CIMA ), Universidad de Navarra [Pamplona] ( UNAV ) -Universidad de Navarra [Pamplona] ( UNAV ), Molecular Microbiology Group ( COMB ), University of the Ruykyus, Laboratory of Biological protection, Kyoto University [Kyoto], Immunologie et Embryologie Moléculaire ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Apoptose, cancer et immunité ( U848 ), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy ( IGR ), Composantes innées de la réponse immunitaire et différenciation ( CIRID ), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Pôle de biologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), School of Medicine, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11), Peter MacCallum Cancer Center, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Division of Hepatology and Gene Therapy (CIMA), Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV)-Universidad de Navarra [Pamplona] (UNAV), Molecular Microbiology Group (COMB), Kyoto University, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Apoptose, cancer et immunité (U848), Institut Gustave Roussy (IGR), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Vougny, Marie-Christine, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adoptive cell transfer, MESH : Aged, MESH : Equipment Design, CD8-Positive T-Lymphocytes, MESH: Catheterization, Interleukin-23, MESH: Long-Term Care, Mice, 0302 clinical medicine, MESH : Catheterization, T-Lymphocyte Subsets, MESH: Nursing, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Interferon gamma, MESH: Quality of Health Care, MESH: Professional Review Organizations, MESH: Aged, MESH : Gels, 0303 health sciences, Mice, Inbred BALB C, Cell Death, Interleukin-17, MESH : Methylene Blue, MESH : Quality of Health Care, Receptors, Antigen, T-Cell, gamma-delta, Chemotherapy regimen, MESH: Transplantation, Autologous, 3. Good health, MESH: Cosmetic Techniques, Treatment Outcome, medicine.anatomical_structure, MESH : Cadaver, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunogenic cell death, Sarcoma, Experimental, Interleukin 17, MESH : Dissection, MESH : Long-Term Care, MESH: Nursing Care, MESH: Adipose Tissue, medicine.drug, Signal Transduction, MESH : Transplantation, Autologous, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Feasibility Studies, MESH: Gels, T cell, MESH : Male, Immunology, MESH: Dissection, Antineoplastic Agents, Biology, MESH : Nursing, MESH : Adipose Tissue, Article, MESH : Facial Muscles, 03 medical and health sciences, Interferon-gamma, Lymphocytes, Tumor-Infiltrating, Immune system, Antigen, Cell Line, Tumor, MESH: Patient Care Planning, medicine, MESH: Cadaver, Animals, MESH : Patient Care Planning, 030304 developmental biology, MESH: Humans, business.industry, MESH: Facial Muscles, T-cell receptor, MESH : Humans, Correction, MESH: Male, Mice, Inbred C57BL, MESH : Cosmetic Techniques, Doxorubicin, Cancer research, MESH : Nursing Care, MESH : Professional Review Organizations, business, MESH: Feasibility Studies, CD8, 030215 immunology, MESH: Methylene Blue, MESH: Equipment Design
Abstract

IL-17 production by γδ T cells is required for tumor cell infiltration by IFN-γ–producing CD8+ T cells and inhibition of tumor growth in response to anthracyclines., By triggering immunogenic cell death, some anticancer compounds, including anthracyclines and oxaliplatin, elicit tumor-specific, interferon-γ–producing CD8+ αβ T lymphocytes (Tc1 CTLs) that are pivotal for an optimal therapeutic outcome. Here, we demonstrate that chemotherapy induces a rapid and prominent invasion of interleukin (IL)-17–producing γδ (Vγ4+ and Vγ6+) T lymphocytes (γδ T17 cells) that precedes the accumulation of Tc1 CTLs within the tumor bed. In T cell receptor δ−/− or Vγ4/6−/− mice, the therapeutic efficacy of chemotherapy was compromised, no IL-17 was produced by tumor-infiltrating T cells, and Tc1 CTLs failed to invade the tumor after treatment. Although γδ T17 cells could produce both IL-17A and IL-22, the absence of a functional IL-17A–IL-17R pathway significantly reduced tumor-specific T cell responses elicited by tumor cell death, and the efficacy of chemotherapy in four independent transplantable tumor models. Adoptive transfer of γδ T cells restored the efficacy of chemotherapy in IL-17A−/− hosts. The anticancer effect of infused γδ T cells was lost when they lacked either IL-1R1 or IL-17A. Conventional helper CD4+ αβ T cells failed to produce IL-17 after chemotherapy. We conclude that γδ T17 cells play a decisive role in chemotherapy-induced anticancer immune responses.

Published
2011

31. Coenzyme Q as an antiadipogenic factor

Author

Luc Van Gaal, Anne Galinier, Louis Casteilla, Luc Pénicaud, Bart Staels, Sandy Bour, Maria-Carmen Carmona, Sylvie Caspar-Bauguil, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Antwerp University Hospital [Edegem] (UZA), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Antwerp University Hospital, Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Hôpital de Rangueil-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neurobiologie, plasticité tissulaire et métabolisme énergétique ( NPTME ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Antwerp University Hospital [Edegem], Récepteurs nucléaires, maladies cardiovasculaires et diabète ( EGID ), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS )

Subjects
Male, Antioxidant, muscle, medicine.medical_treatment, Cellular differentiation, coq(10) deficiency, MESH : Adipocytes, White adipose tissue, Biochemistry, Antioxidants, Mice, 0302 clinical medicine, q(10) deficiency, Adipocyte, MESH: Animals, Enzyme Inhibitors, MESH: Mice, Obese, MESH : Body Weight, General Environmental Science, 0303 health sciences, Adipogenesis, MESH : Adipogenesis, food and beverages, MESH : Mice, Obese, MESH : Ubiquinone, MESH : alpha-Tocopherol, MESH : Antioxidants, MESH : Cell Differentiation, MESH: Adipose Tissue, medicine.medical_specialty, MESH: Alkyl and Aryl Transferases, MESH : Adipose Tissue, MESH : Quinones, 03 medical and health sciences, Humans, Molecular Biology, MESH: Adipocytes, Alkyl and Aryl Transferases, MESH: Humans, [ SDV ] Life Sciences [q-bio], MESH : Humans, MESH: Antioxidants, MESH : Organ Size, MESH: Body Weight, MESH: Cell Line, Mice, Inbred C57BL, Endocrinology, chemistry, Human medicine, Reactive Oxygen Species, MESH: Female, MESH : Dietary Fats, 030217 neurology & neurosurgery, MESH : Cell Line, obesity, Physiology, Ubiquinone, MESH: Organ Size, [SDV]Life Sciences [q-bio], Clinical Biochemistry, alpha-Tocopherol, MESH : Reactive Oxygen Species, Adipose tissue, Mice, Obese, rosiglitazone, chemistry.chemical_compound, Adipocytes, oxidative stress, MESH: Obesity, MESH : Female, MESH: Ubiquinone, Quinones, MESH: Reactive Oxygen Species, Cell Differentiation, Organ Size, adipose tissue, MESH: alpha-Tocopherol, MESH: Enzyme Inhibitors, MESH: Dietary Fats, MESH : Obesity, Female, MESH: Cell Differentiation, uncoupling protein 2, MESH : Male, MESH : Mice, Inbred C57BL, mitochondrial encephalomyopathy, Biology, MESH: Quinones, Cell Line, MESH: Mice, Inbred C57BL, Internal medicine, MESH : Mice, expression, medicine, Animals, MESH: Mice, MESH : Alkyl and Aryl Transferases, 030304 developmental biology, MESH : Enzyme Inhibitors, Body Weight, Cell Biology, Dietary Fats, MESH: Male, Cell culture, Coenzyme Q – cytochrome c reductase, General Earth and Planetary Sciences, MESH : Animals, MESH: Adipogenesis
Abstract

WOS: 000285876900007; International audience; Coenzyme Q (CoQ) is not only the single antioxidant synthesized in humans but also an obligatory element of mitochondrial functions. We have previously reported CoQ deficiency in white adipose tissue of ob/ob mice. We sought to determine (i) whether this deficit exists in all species and its relevance in human obesity and (ii) to what extent CoQ could be involved in adipocyte differentiation. Here we identified in rodents as well as in humans a specific very strong nonlinear negative correlation between CoQ content in subcutaneous adipose tissue and obesity indexes. This striking correlation reveals a threshold value similar in both species. This relative deficit in CoQ content in adipose tissue rapidly took place during the time course of high-fat-diet-induced obesity in mice. Adipocyte differentiation was assessed in vitro using the preadipocyte 3T3-F442A cell line. When CoQ synthesis was inhibited by a pharmacological approach using chlorobenzoic acid, this strongly triggered adipose differentiation. In contrast, adipogenesis was strongly inhibited when a long-term increase in CoQ content was obtained by overexpressing human 4-hydroxy benzoate acid polyprenyltransferase gene. Altogether, these data suggest that a strict level of CoQ remains essential for adipocyte differentiation, and its impairment is associated with obesity.

Published
2011

32. Is Crohn’s creeping fat an adipose tissue?

Author

Jean-Pierre Segain, Laurent Ferrier, Isabelle Olivier, Philippe Valet, Valérie Bézirard, Sylvain Kirzin, Robert Ducroc, Helene Eutamene, J Moreau, Christel Cartier, Justine Bertrand-Michel, Isabelle Castan-Laurell, Jean-Pierre Duffas, Hervé Guillou, Vassilia Theodorou, Guillaume Portier, Eutamene, Hélène, Unité de nutrition et neuro-gastroentérologie, Institut National de la Recherche Agronomique (INRA)-PRES Université de Toulouse-El-Purpan-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacologie et Toxicologie, Institut National de la Recherche Agronomique (INRA), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Chirurgie Générale et Digestive [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Chirurgie Générale et Digestive [Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, Physiologie des Adaptations Nutritionnelles (PhAN), Neuro-Gastroentérologie et Nutrition (NGN), Institut National de la Recherche Agronomique (INRA)-Ecole supérieure d'agriculture de Purpan (ESAP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Simon, Marie Francoise

Subjects
Male, Pathology, [SDV]Life Sciences [q-bio], Adipose tissue, Cystic fibrosis, Immunoenzyme Techniques, Mice, 0302 clinical medicine, Crohn Disease, MESH: Peroxidase, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Colitis, Immunology and Allergy, Medicine, MESH: Animals, Mesentery, 0303 health sciences, Crohn's disease, Mice, Inbred BALB C, Reverse Transcriptase Polymerase Chain Reaction, Gastroenterology, MESH: Enzyme-Linked Immunosorbent Assay, Colitis, Lipids, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Adipose Tissue, 030211 gastroenterology & hepatology, medicine.symptom, MESH: Adipose Tissue, MESH: Dinitrofluorobenzene, medicine.medical_specialty, Blotting, Western, MESH: Mice, Inbred BALB C, creeping fat, mesenteric adipose tissue, Crohn’s disease, animal model, Inflammation, Enzyme-Linked Immunosorbent Assay, 03 medical and health sciences, Animal model, MESH: Blotting, Western, Animals, Humans, RNA, Messenger, MESH: Immunoenzyme Techniques, MESH: Mesentery, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, Peroxidase, MESH: Humans, MESH: Crohn Disease, business.industry, Body Weight, medicine.disease, MESH: Lipids, MESH: Male, MESH: Body Weight, Mesenteric adipose tissue, Dinitrofluorobenzene, business, Human Pathology
Abstract

International audience; BACKGROUND: In human pathology, the "creeping fat" (CF) of the mesentery is unique to Crohn's disease (CD). CF is usually referred to as an ectopic extension of mesenteric adipose tissue (MAT). However, since no animal model developing CF has ever been established, very little is known about this type of fat-depot expansion and its role in the development of the disease. METHODS: We developed and standardized an experimental protocol in mice that reproducibly induces CF development when a severe colonic inflammation is obtained by intracolonic instillation of DNBS. RESULTS: Macro-microscopic observations revealed a fatty appearance of CF. Yet when compared to MAT from the same animals, CF contains very little triglycerides, few adipocytes, and we observed a very low expression and protein levels of both adipose markers (hormone-sensitive lipase, perilipin) and adipocytokines (leptin, adiponectin). The decreased expression of perilipin in CF was also observed by immunohistochemistry. Conversely, the expression of proinflammatory and fibrous markers (Pref-1) was much higher in CF than in MAT. These observations were fully consistent with those made on CF recovered from five CD patients and compared with subcutaneous and mesenteric fat from the same patients. CONCLUSIONS: Altogether, this work reports an original experimental mice model of CF. In this model we establish for the first time that CF only occurs in severe colonic inflammation and shows an inflammatory, fibrous but not an adipose pattern.

Published
2011

33. Relationships between adipose tissues and brain: what do we learn from animal studies?

Author

Luc Pénicaud, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS )

Subjects
medicine.medical_specialty, MESH: Mice, Transgenic, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, Diabetes and Metabolism, Central nervous system, Adipokine, Adipose tissue, Mice, Transgenic, White adipose tissue, Biology, MESH : Adipose Tissue, Energy homeostasis, Mice, MESH: Brain, Endocrinology, MESH : Lipid Metabolism, Internal medicine, MESH : Mice, Brown adipose tissue, Internal Medicine, medicine, Animals, Humans, Lipolysis, MESH: Animals, MESH: Mice, MESH: Lipid Metabolism, MESH: Humans, Leptin, MESH : Humans, Brain, General Medicine, Lipid Metabolism, MESH : Mice, Transgenic, MESH : Models, Animal, medicine.anatomical_structure, Adipose Tissue, MESH : Brain, MESH: Models, Animal, Models, Animal, MESH : Animals, Neuroscience, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Adipose Tissue
Abstract

International audience; Over the last decades, more and more data supporting the importance of the relationships between the brain and adipose tissues (white and brown) in regards of body weight regulation and energy homeostasis have been published. Indeed the brain via the autonomic nervous system participates to the regulation of different parameters such as the metabolic (lipolysis, lipogenesis and thermogeneis), and secretory (leptin and other adipokines) activities but also plasticity (proliferation differentiation and apoptosis) of adipose tissues. In turn the various fat pads will send information via sensory innervation of white adipose tissue as well as metabolic and hormonal signals acting directly on some brain areas. Altogether these results showed the presence of a neural feedback loop between adipose tissues and the brain which plays a major role in the regulation of energy homeostasis and as been shown to vary according to physiological and pathological states.

Published
2010

34. Analysis of lifestyle and metabolic predictors of visceral obesity with Bayesian Networks

Author

Sérgio Rodrigues de Morais, André Tchernof, Alex Aussem, Sophie Rome, Laboratoire d'Informatique pour l'Entreprise et les Systèmes de Production (LIESP), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Endocrinology and Genomics, Laval University [Québec], Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), André Tchernof is the recipient of a Fonds de la recherche en santé du Québec Senior investigator scholarship., Université Laval [Québec] (ULaval), BMC, Ed., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)

Subjects
Adipose Tissue, Algorithms, Bayes Theorem, Female, Gene Expression Profiling, Humans, Life Style, Obesity, Abdominal, Inference, 02 engineering and technology, computer.software_genre, Bioinformatics, Biochemistry, Bayes' theorem, Structural Biology, 0202 electrical engineering, electronic engineering, information engineering, lcsh:QH301-705.5, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Applied Mathematics, MESH: Life Style, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, Obesity, Abdominal, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Bio-informatique, lcsh:R858-859.7, 020201 artificial intelligence & image processing, Biological plausibility, MESH: Adipose Tissue, Research Article, MESH: Bayes Theorem, Bayesian probability, Sample (statistics), MESH: Algorithms, Biology, Machine learning, lcsh:Computer applications to medicine. Medical informatics, MESH: Obesity, Abdominal, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Molecular Biology, 030304 developmental biology, MESH: Humans, business.industry, Robustness (evolution), Bayesian network, SDV:BBM:GTP, Constraint (information theory), lcsh:Biology (General), Artificial intelligence, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, computer, SDV:BIBS, MESH: Female
Abstract

Background The aim of this study was to provide a framework for the analysis of visceral obesity and its determinants in women, where complex inter-relationships are observed among lifestyle, nutritional and metabolic predictors. Thirty-four predictors related to lifestyle, adiposity, body fat distribution, blood lipids and adipocyte sizes have been considered as potential correlates of visceral obesity in women. To properly address the difficulties in managing such interactions given our limited sample of 150 women, bootstrapped Bayesian networks were constructed based on novel constraint-based learning methods that appeared recently in the statistical learning community. Statistical significance of edge strengths was evaluated and the less reliable edges were pruned to increase the network robustness. To allow accessible interpretation and integrate biological knowledge into the final network, several undirected edges were afterwards directed with physiological expertise according to relevant literature. Results Extensive experiments on synthetic data sampled from a known Bayesian network show that the algorithm, called Recursive Hybrid Parents and Children (RHPC), outperforms state-of-the-art algorithms that appeared in the recent literature. Regarding biological plausibility, we found that the inference results obtained with the proposed method were in excellent agreement with biological knowledge. For example, these analyses indicated that visceral adipose tissue accumulation is strongly related to blood lipid alterations independent of overall obesity level. Conclusions Bayesian Networks are a useful tool for investigating and summarizing evidence when complex relationships exist among predictors, in particular, as in the case of multifactorial conditions like visceral obesity, when there is a concurrent incidence for several variables, interacting in a complex manner. The source code and the data sets used for the empirical tests are available at http://www710.univ-lyon1.fr/~aaussem/Software.html.

Published
2010

35. Chondrogenic potential of bone marrow- and adipose tissue-derived adult human mesenchymal stem cells

Author

Perrier-Groult, Emeline, Ronzière, F, Perrier, E., Mallein-Gerin, F., Freyria, Anne-Marie, Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Male, Cellular differentiation, [SDV]Life Sciences [q-bio], Cell Culture Techniques, MESH: Tissue Engineering, 0302 clinical medicine, Cells, Cultured, Stem cell transplantation for articular cartilage repair, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: Bone Marrow Cells, Cell Differentiation, General Medicine, Middle Aged, Oxygen tension, Cell biology, medicine.anatomical_structure, Adipose Tissue, 030220 oncology & carcinogenesis, Female, Stem cell, Chondrogenesis, MESH: Adipose Tissue, MESH: Chondrogenesis, Adult stem cell, MESH: Cells, Cultured, Adult, MESH: Cell Differentiation, Biomedical Engineering, Bone Marrow Cells, Biology, Chondrocyte, Biomaterials, 03 medical and health sciences, Chondrocytes, MESH: Chondrocytes, medicine, Humans, Aged, 030304 developmental biology, MESH: Cell Culture Techniques, MESH: Humans, Tissue Engineering, Mesenchymal stem cell, Mesenchymal Stem Cells, MESH: Adult, MESH: Male, MESH: Mesenchymal Stem Cells, MESH: Female
Abstract

International audience; Regarding cartilage repair, tissue engineering is currently focusing on the use of adult mesenchymal stem cells (MSC) as an alternative to autologous chondrocytes. The potential of stem cells from various tissues to differentiate towards the chondrogenic phenotype has been investigated and it appears that the most common and studied sources are bone marrow (BM) and adipose tissue (AT) for historical and easy access reasons. In addition to three dimensional environment, the presence of member(s) of the transforming growth factor (TGF-β family and low oxygen tension have been reported to promote the in vitro differentiation of MSCs. Our work aimed at characterizing and comparing the degree of chondrogenic differentiation of MSCs isolated from BM and AT cultured in the same conditions. We also further aimed at and at determining whether hypoxia (2% oxygen) could affect the chondrogenic potential of AT-MSCs. Cells were first expanded in the presence of FGF-2, then harvested and centrifuged to allow formation of cell pellets, which were cultured in the presence of TGF-β3 and/or Bone Morphogenetic Protein-2 (BMP-2) and with 2 or 20% oxygen tension, for 24 days. Markers of the chondrocyte (COL2A1, AGC1, Sox9) and hypertrophic chondrocyte (COL10A1, MMP-13) were monitored by real-time PCR and/or by immunohistological staining. Our data show that BMP-2/TGF-β3 combination is the best culture condition to induce the chondrocyte phenotype in pellet cultures of BM and AT-MSCs. Particularly, a switch in the expression of the pre-chondrogenic type IIA form to the cartilage-specific type IIB form of COL2A1 was observed. A parallel increase in gene expression of COL10A1 and MMP-13 was also recorded. However when AT-MSCs were cultured in hypoxia, the expression of markers of hypertrophic chondrocytes decreased when BMP-2/TGF-β3 were present in the medium. Thus it seems that hypoxia participates to the control of AT-MSCs chondrogenesis. Altogether, these cellular model systems will help us to investigate further the potential of different adult stem cells for cartilage engineering.

Published
2010

36. Proteasomal degradation of retinoid X receptor alpha reprograms transcriptional activity of PPARgamma in obese mice and humans

Author

François Pattou, Julie Dumont, Emmanuel Bouchaert, Alain Ktorza, Philippe Lefebvre, Catherine Dacquet, Aurore Guédin, Luc Pénicaud, Yacir Benomar, Audrey Langlois, Bruno Lefebvre, Louis Casteilla, Bart Staels, Nathalie Hennuyer, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Division of Meabolic Diseases, Institut de Recherches Servier, Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31] (LMPM), IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Thérapie cellulaire du diabète, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Division of Metabolic Diseases, Derudas, Marie-Hélène, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Transcription, Genetic, Peroxisome proliferator-activated receptor, Mice, Obese, White adipose tissue, MESH: Thiazolidinediones, MESH: Retinoid X Receptor alpha, Mice, 0302 clinical medicine, MESH: Obesity, MESH: Animals, MESH: Mice, Obese, chemistry.chemical_classification, 0303 health sciences, MESH: Proteasome Endopeptidase Complex, General Medicine, MESH: Gene Expression Regulation, MESH: Insulin Resistance, Adipose Tissue, Signal transduction, Ubiquitin Thiolesterase, MESH: Adipose Tissue, Research Article, Agonist, medicine.medical_specialty, Proteasome Endopeptidase Complex, medicine.drug_class, 030209 endocrinology & metabolism, Retinoid X receptor, Biology, Rosiglitazone, 03 medical and health sciences, Downregulation and upregulation, Internal medicine, 3T3-L1 Cells, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, MESH: Mice, 030304 developmental biology, Thyroid hormone receptor, Retinoid X Receptor alpha, MESH: Humans, Retinoid X receptor alpha, MESH: Transcription, Genetic, MESH: Ubiquitin Thiolesterase, MESH: 3T3-L1 Cells, MESH: Male, PPAR gamma, Endocrinology, chemistry, Gene Expression Regulation, MESH: PPAR gamma, Thiazolidinediones, Insulin Resistance
Abstract

International audience; Obese patients have chronic, low-grade inflammation that predisposes to type 2 diabetes and results, in part, from dysregulated visceral white adipose tissue (WAT) functions. The specific signaling pathways underlying WAT dysregulation, however, remain unclear. Here we report that the PPARgamma signaling pathway operates differently in the visceral WAT of lean and obese mice. PPARgamma in visceral, but not subcutaneous, WAT from obese mice displayed increased sensitivity to activation by its agonist rosiglitazone. This increased sensitivity correlated with increased expression of the gene encoding the ubiquitin hydrolase/ligase ubiquitin carboxyterminal esterase L1 (UCH-L1) and with increased degradation of the PPARgamma heterodimerization partner retinoid X receptor alpha (RXRalpha), but not RXRbeta, in visceral WAT from obese humans and mice. Interestingly, increased UCH-L1 expression and RXRalpha proteasomal degradation was induced in vitro by conditions mimicking hypoxia, a condition that occurs in obese visceral WAT. Finally, PPARgamma-RXRbeta heterodimers, but not PPARgamma-RXRalpha complexes, were able to efficiently dismiss the transcriptional corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) upon agonist binding. Increasing the RXRalpha/RXRbeta ratio resulted in increased PPARgamma responsiveness following agonist stimulation. Thus, the selective proteasomal degradation of RXRalpha initiated by UCH-L1 upregulation modulates the relative affinity of PPARgamma heterodimers for SMRT and their responsiveness to PPARgamma agonists, ultimately activating the PPARgamma-controlled gene network in visceral WAT of obese animals and humans.

Published
2010

37. CB1 antagonism exerts specific molecular effects on visceral and subcutaneous fat and reverses liver steatosis in diet-induced obese mice

Author

Louiza Djaouti, Pascal Degrace, Joseph Gresti, Laurent Demizieux, Tony Jourdan, Bruno Vergès, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), This work was supported by grants from sanofi-aventisand the Re´gion Bourgogne., Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), and DEGRACE, Pascal

Subjects
Sucrose, MESH : Fatty Liver, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, MESH: Organ Size, MESH : Piperidines, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Adipose tissue, Mice, Obese, MESH: Receptor, Cannabinoid, CB1, MESH : Pyrazoles, chemistry.chemical_compound, Mice, Piperidines, Receptor, Cannabinoid, CB1, Adipocyte, MESH: Obesity, MESH: Animals, MESH: Animal Feed, MESH: Fatty Liver, MESH: Mice, Obese, MESH : Body Weight, MESH : Gene Expression Regulation, Fatty liver, MESH: Apolipoproteins A, Organ Size, MESH: Adiponectin, MESH: Apolipoproteins B, MESH : Mice, Obese, MESH: Gene Expression Regulation, MESH: Piperidines, MESH : Animal Feed, Adipose Tissue, Liver, Original Article, lipids (amino acids, peptides, and proteins), MESH : Obesity, Adiponectin, Rimonabant, Obesity Studies, MESH: Adipose Tissue, MESH : Cannabinoid Receptor Antagonists, medicine.medical_specialty, Biology, MESH : Receptor, Cannabinoid, CB1, MESH : Adipose Tissue, MESH : Diet, MESH: Diet, Internal medicine, MESH : Mice, Internal Medicine, medicine, Animals, Obesity, MESH: Cannabinoid Receptor Antagonists, Cannabinoid Receptor Antagonists, MESH: Mice, Apolipoproteins A, Apolipoproteins B, MESH : Adiponectin, Insulin, Body Weight, MESH: Sucrose, MESH : Liver, Lipid metabolism, MESH : Apolipoproteins B, MESH : Organ Size, MESH : Apolipoproteins A, medicine.disease, Animal Feed, MESH : Sucrose, Diet, MESH: Body Weight, Fatty Liver, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, chemistry, Gene Expression Regulation, Pyrazoles, Hepatic lipase, MESH : Animals, Diet-induced obese, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Pyrazoles, MESH: Liver
Abstract

OBJECTIVE The beneficial effects of the inactivation of endocannabinoid system (ECS) by administration of antagonists of the cannabinoid receptor (CB) 1 on several pathological features associated with obesity is well demonstrated, but the relative contribution of central versus peripheral mechanisms is unclear. We examined the impact of CB1 antagonism on liver and adipose tissue lipid metabolism in a mouse model of diet-induced obesity. RESEARCH DESIGN AND METHODS Mice were fed either with a standard diet or a high-sucrose high-fat (HSHF) diet for 19 weeks and then treated with the CB1-specific antagonist SR141716 (10 mg · kg−1 · day−1) for 6 weeks. RESULTS Treatment with SR141716 reduced fat mass, insulin levels, and liver triglycerides primarily increased by HSHF feeding. Serum adiponectin levels were restored after being reduced in HSHF mice. Gene expression of scavenger receptor class B type I and hepatic lipase was induced by CB1 blockade and associated with an increase in HDL-cholesteryl ether uptake. Concomitantly, the expression of CB1, which was strongly increased in the liver and adipose tissue of HSHF mice, was totally normalized by the treatment. Interestingly, in visceral but not subcutaneous fat, genes involved in transport, synthesis, oxidation, and release of fatty acids were upregulated by HSHF feeding, while this effect was counteracted by CB1 antagonism. CONCLUSIONS A reduction in the CB1-mediated ECS activity in visceral fat is associated with a normalization of adipocyte metabolism, which may be a determining factor in the reversion of liver steatosis induced by treatment with SR141716.

Published
2010

38. Human lipodystrophies: genetic and acquired diseases of adipose tissue

Author

Vé Ronique Béréziat, Martine Caron-Debarle, Corinne Vigouroux, Jacqueline Capeau, Jocelyne Magré, Olivier Lascols, Bénédicte Antoine, Jean-Philippe Bastard, Claire Lagathu, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The authors were supported by grants from INSERM, ANRS, SIDACTION, ALFEDIAM, and the European Eurolaminopathy network, Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Vigouroux, Corinne, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Premature aging, medicine.medical_specialty, Lipodystrophy, MESH: 1-Acylglycerol-3-Phosphate O-Acyltransferase, MESH: Lamin Type A, Adipose tissue, 030209 endocrinology & metabolism, Biology, Article, Seipin, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, MESH: Lipodystrophy, Internal medicine, medicine, Humans, Lipoatrophy, 030304 developmental biology, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Progeria, MESH: Humans, Partial Lipodystrophy, 1-Acylglycerol-3-Phosphate O-Acyltransferase, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Lamin Type A, medicine.disease, 3. Good health, PPAR gamma, Endocrinology, Adipose Tissue, MESH: PPAR gamma, MESH: Adipose Tissue
Abstract

International audience; Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2(AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARgamma. Importantly, lamin A/Cmutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their etiology is generally unknown, they could be associated with signs of autoimmunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first-generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardiovascular and hepatic complications.

Published
2010

39. Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake

Author

Adriana Márquez-Quiñones, Dominique Langin, Karine Clément, Wim H. M. Saris, Teodora Handjieva-Darlenska, Marion Combes, Ping Wang, Andreas Pfeiffer, Dimitris K. Babalis, David M. Mutch, Thomas Meinert Larsen, Susan A. Jebb, Claus Holst, Edwin C. M. Mariman, Hubert Vidal, Arne Astrup, Nathalie Viguerie, Pavla Kalouskova, Balbine Roussel, Cyrille Debard, J. Alfredo Martínez, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Santé Publique et Informatique Médicale (SPIM), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Human Health and Nutritional Sciences, University of Guelph, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Department of Human Biology, Maastricht University [Maastricht], Institute of Preventive Medicine, Copenhagen University Hospitals, Department of Physiology and Nutrition, Universidad de Navarra [Pamplona] (UNAV), Department of Pharmacology and Toxicology, Medical Faculty, Medical University, Obesity Management Centre, Institute of Endocrinology, Human Nutrition Research, Elsie Widdowson Laboratory, Department of Internal Medicine, University Hospital of Heraklion, Department of Clinical Nutrition, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Human Nutrition, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], European Community [FP6-513946], Institut National de la Sante et de la Recherche Medicale, Region Midi-Pyrenees, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Santé Publique et Informatique Médicale ( SPIM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Universidad de Navarra [Pamplona] ( UNAV ), Charité Universitäts Medizin Berlin, University of Copenhagen ( KU ), Centre de Recherche en Nutrition Humaine d'Ile-de-France ( CRNH-IDF ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Institut National Agronomique Paris-Grignon ( INA P-G ) -CETAF-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Paris 13 (UP13)-CETAF-Institut National Agronomique Paris-Grignon (INA P-G)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut de Veille Sanitaire (INVS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humane Biologie, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - R1 - Metabolic Syndrome

Subjects
MESH: Treatment Failure, Blood Pressure, MESH: Energy Intake, Transcriptome, 0302 clinical medicine, HIGH-PROTEIN, Models, MESH: Models, Genetic, GENE-EXPRESSION, Oligonucleotide Array Sequence Analysis, MESH: Treatment Outcome, 0303 health sciences, MACRONUTRIENT, Reducing, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH: Blood Pressure, MESH: Follow-Up Studies, LOW-FAT, Gene expression profiling, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, Adipose Tissue, MESH: Adipose Tissue, medicine.medical_specialty, Diet, Reducing, LOSS MAINTENANCE, MESH : Adipose Tissue, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Weight Loss, MESH : Treatment Failure, Genetic, Humans, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Humans, MESH : Gene Expression Profiling, MESH : Humans, MESH : Follow-Up Studies, MESH: Adult, Anthropometry, medicine.disease, Obesity, Endocrinology, MICROARRAY DATA, Energy intake, MESH: Female, Calorie, Time Factors, Medicine (miscellaneous), Adipose tissue, MESH : Models, Genetic, HUMAN OBESITY, Weight loss, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : RNA, MESH: Obesity, MESH : Female, Treatment Failure, MESH : Diet, Reducing, 2. Zero hunger, MESH: Diet, Reducing, Nutrition and Dietetics, Reverse Transcriptase Polymerase Chain Reaction, MESH : Adult, ADIPOCYTES, Glycemic index, Treatment Outcome, MESH : Obesity, Female, medicine.symptom, Dieting, MESH : Time Factors, Adult, 030209 endocrinology & metabolism, MESH : Treatment Outcome, Biology, DiOGenes, MESH: RNA, Internal medicine, Weight Loss, medicine, MESH : Blood Pressure, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, LOSS DIETS, Models, Genetic, Gene Expression Profiling, MESH: Time Factors, MESH : Energy Intake, Diet, MESH: Oligonucleotide Array Sequence Analysis, GLYCEMIC INDEX, RNA, MESH : Weight Loss, Energy Intake, Follow-Up Studies
Abstract

Background: The mechanisms underlying body weight evolution after diet-induced weight loss are poorly understood. Objective: We aimed to identify and characterize differences in the subcutaneous adipose tissue (SAT) transcriptome of subjects with different weight changes after energy restriction-induced weight loss during 6 mo on 4 different diets. Design: After an 8-wk low-calorie diet (800 kcal/d), we randomly assigned weight-reduced obese subjects from 8 European countries to receive 4 diets that differed in protein and glycemic index content. In addition to anthropometric and plasma markers, SAT biopsies were taken at the beginning [clinical investigation day (CID) 2] and end (CID3) of the weight follow-up period. Microarray analysis was used to define SAT gene expression profiles at CID2 and CID3 in 22 women with continued weight loss (successful group) and in 22 women with weight regain (unsuccessful group) across the 4 dietary arms. Results: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather than to differences in dietary macronutrient content. An analysis of covariance with total energy intake as a covariate identified 1338 differentially expressed genes. Cellular growth and proliferation, cell death, cellular function, and maintenance were the main biological processes represented in SAT from subjects who regained weight. Mitochondrial oxidative phosphorylation was the major pattern associated with continued weight loss. Conclusions: The ability to control body weight loss independent of energy intake or diet composition is reflected in the SAT transcriptome. Although cell proliferation may be detrimental, a greater mitochondrial energy gene expression is suggested as being beneficial for weight control. This trial was registered at clinicaltrials.gov as NCT00390637. © 2010 American Society for Nutrition.

Published
2010

40. HMGA2-NFIB fusion in a pediatric intramuscular lipoma: a novel case of NFIB alteration in a large deep-seated adipocytic tumor

Author

Florence Pedeutour, Carla Fernandez, Géraldine Hery, Hélène Zattara, Frédérique Keslair, Anne Pierron, Esma Saada, Laboratory of Solid Tumors Genetics, Nice University Hospital, Institut de signalisation, biologie du développement et cancer (ISBDC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Pathology and Neuropathology, University of the Mediterranean, Laboratoire de Physiopathologie Respiratoire (UPRES EA 2201), Université de la Méditerranée - Aix-Marseille 2-Institut Fédératif de Recherches Jean ROCHE (IFR 11)-Faculté de Médecine Nord, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)

Subjects
Male, Cancer Research, Pathology, Oncogene Proteins, Fusion, MESH: NFI Transcription Factors, Exon, 0302 clinical medicine, MESH: Child, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: In Situ Hybridization, Fluorescence, Child, [SDV.BDD]Life Sciences [q-bio]/Development Biology, In Situ Hybridization, Fluorescence, Genetics, 0303 health sciences, biology, medicine.diagnostic_test, Reverse Transcriptase Polymerase Chain Reaction, Lipoma, 3. Good health, Adipose Tissue, NFIB, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Chromosomal region, Sequence Analysis, MESH: Adipose Tissue, medicine.medical_specialty, Chimeric gene, 03 medical and health sciences, MESH: Sequence Analysis, HMGA2, medicine, otorhinolaryngologic diseases, Humans, Molecular Biology, 030304 developmental biology, MESH: Lipoma, MESH: Humans, MESH: Cytogenetic Analysis, HMGA2 Protein, Intramuscular Lipoma, medicine.disease, MESH: Male, body regions, NFI Transcription Factors, biology.protein, MESH: HMGA2 Protein, Fluorescence in situ hybridization, MESH: Oncogene Proteins, Fusion
Abstract

International audience; Lipomas are frequently characterized by aberrations of the 12q13 approximately q15 chromosomal region and often by rearrangements of the HMGA2 gene. These rearrangements include the formation of chimeric genes that fuse the 5' region of HMGA2 with a variety of partners, such as LPP (3q28) or NFIB (9p22). We describe here the fourth reported case of lipoma showing a HMGA2-NFIB fusion, and the first one in a child. We found a translocation t(9;12)(p22;q14) in a deep-seated intramuscular lipoma occurring in the buttock of a 5-year-old boy. By fluorescence in situ hybridization and reverse-transcription polymerase chain reaction, we have shown that the translocation t(9;12) resulted in an in-frame fusion of the first four exons of HMGA2 with the last exon of NFIB. Intramuscular lipomas are very rare in childhood. Our results confirm that lipomas containing NFIB rearrangements may be related to peculiar clinicohistologic features, including large size, deep situation, infiltration of surrounding muscles, or precocious occurrence. Both the truncation of HMGA2 and the nature of its fusion partner gene might be relevant in the adipose tissue tumorigenesis.

Published
2009

41. The role of sirtuins in the control of metabolic homeostasis

Author

Johan Auwerx, Jiujiu Yu, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Clinique de la Souris (ICS), and Peney, Maité

Subjects
SIRT3, MESH: Mitochondria, Longevity, Regulator, MESH: Insulin, Nicotinamide adenine dinucleotide, SIRT2, Article, General Biochemistry, Genetics and Molecular Biology, chemistry.chemical_compound, Sirtuin 2, Sirtuin 1, History and Philosophy of Science, Homeostasis, Humans, Insulin, Sirtuins, MESH: Thermogenesis, Muscle, Skeletal, MESH: Muscle, Skeletal, MESH: Humans, biology, General Neuroscience, MESH: Energy Metabolism, MESH: NAD, Thermogenesis, MESH: Sirtuins, NAD, Lipids, MESH: Lipids, Mitochondria, MESH: Glucose, Glucose, Adipose Tissue, chemistry, Biochemistry, MESH: Homeostasis, MESH: Longevity, Metabolic control analysis, Sirtuin, biology.protein, NAD+ kinase, Energy Metabolism, MESH: Adipose Tissue
Abstract

International audience; Recently the function of the sirtuin family, named after their homology to the Saccharomyces cerevisiae gene silent information regulator 2 (Sir2), has received a lot of attention, as their beneficial impact on longevity was linked to their effects on metabolic control. All sirtuins require nicotinamide adenine dinucleotide (NAD(+)) for their deacetylase or ADP-ribosyl transferase activity, linking their function tightly to cellular energy levels. SIRT1, the founding member of the sirtuin family, modulates many aspects of glucose and lipid homeostasis in almost all key metabolic tissues. Other members including SIRT2, SIRT3, and SIRT4 are also implicated in various metabolic processes. Here, we review the recent data related to the role of sirtuins in the control of metabolic homeostasis and possible underlying molecular mechanisms.

Published
2009

42. CXC ligand 5 is an adipose-tissue derived factor that links obesity to insulin resistance

Author

Julien Schmidt, Lluis Fajas, Eric Renard, Gökhan S. Hotamisligil, Dominique Langin, Gwendal Lazennec, Anna Gumà, Irena Iankova, Hiroyasu Yamamoto, Rosario Sanches, Antonio Vidal-Puig, Carine Chavey, Jacques Teyssier, Robert M. Strieter, Bénédicte Jardin-Watelet, Sylviane Lagarrigue, Jean-Sébastien Annicotte, Antoinette Tuthill, Michaela Vitkova, Chikage Mataki, Cyrielle Clapé, Vladimir Stich, Antonio Zorzano, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Métabolisme et cancer, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Université Montpellier 1 (UM1)-IFR3, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Research in Biomedecine, and Departement de Bioquimina Biologia Molecular, Universitat de Barcelona (UB), Department of Sport Medicine and Obesity Unit, Charles University [Prague] (CU), CNRS/Bio-Rad, Centre National de la Recherche Scientifique (CNRS), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de pharmacologie et innovation dans le diabète (CPID), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Department of Medecine, University of Virginia [Charlottesville], Metabolic Research Laboratories, University of Cambridge [UK] (CAM), Harvard School of Public Health, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, This work was supported by grants of INSERM, Fondation pour la Recherche Médicale (équipe FRM), the European Commission (HEPADIP project, Contract LSHM-CT-2005-018734) and ANR (PHYSIO 2006). C.C is granted by Agence National pour la Recherche. GSH is supported by a grant from the National Institutes of Health USA (DK052539)., Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Modélisation et ingéniérie des systèmes complexes pour le diagnostic (MISCD), BIO-RAD FRANCE HOLDING-Centre National de la Recherche Scientifique (CNRS), University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Le Ster, Yves, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre National de la Recherche Scientifique (CNRS), University of Virginia, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
MESH: Signal Transduction, Chemokine CXCL5, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Physiology, Glucose uptake, HUMDISEASE, Adipose tissue, White adipose tissue, MESH: Thiazolidinediones, Mice, 0302 clinical medicine, Adipose Tissue/cytology/drug effects/*metabolism Animals Chemokine CXCL5/deficiency/genetics/*metabolism Gene Expression Regulation/drug effects Humans *Insulin Resistance Macrophages/drug effects/metabolism Mice Obesity/*metabolism RNA, Messenger/genetics/metabolism Signal Transduction/drug effects Thiazolidinediones/pharmacology Tumor Necrosis Factor-alpha/pharmacology, MESH: Obesity, MESH: Animals, CXC chemokine receptors, Receptor, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Gene Expression Regulation, 3. Good health, MESH: Insulin Resistance, Adipose Tissue, medicine.symptom, MESH: Adipose Tissue, Signal Transduction, medicine.medical_specialty, MESH: Rosiglitazone, MESH: Chemokine CXCL5, 030209 endocrinology & metabolism, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Article, Rosiglitazone, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, RNA, Messenger, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, MESH: Humans, Tumor Necrosis Factor-alpha, Macrophages, MESH: Macrophages, Cell Biology, medicine.disease, Insulin receptor, Endocrinology, Gene Expression Regulation, MESH: Tumor Necrosis Factor-alpha, biology.protein, Thiazolidinediones, Insulin Resistance
Abstract

International audience; We show here high levels of expression and secretion of the chemokine CXC ligand 5 (CXCL5) in the macrophage fraction of white adipose tissue (WAT). Moreover, we find that CXCL5 is dramatically increased in serum of human obese compared to lean subjects. Conversely, CXCL5 concentration is decreased in obese subjects after a weight reduction program, or in obese non-insulin-resistant, compared to insulin-resistant, subjects. Most importantly we demonstrate that treatment with recombinant CXCL5 blocks insulin-stimulated glucose uptake in muscle in mice. CXCL5 blocks insulin signaling by activating the Jak2/STAT5/SOCS2 pathway. Finally, by treating obese, insulin-resistant mice with either anti-CXCL5 neutralizing antibodies or antagonists of CXCR2, which is the CXCL5 receptor, we demonstrate that CXCL5 mediates insulin resistance. Furthermore CXCR2-/- mice are protected against obesity-induced insulin resistance. Taken together, these results show that secretion of CXCL5 by WAT resident macrophages represents a link between obesity, inflammation, and insulin resistance.

Published
2009

43. Secretion of adiponectin multimeric complexes from adipose tissue explants is not modified by very low calorie diet

Author

Lenka Rossmeislová, Zuzana Hnevkovska, Magda Bajzova, Zuzana Kovacova, Jan Polak, Michaela Vitkova, Dominique Langin, Vladimir Stich, Michaela Kovacikova, Eva Klimcakova, Sports Medicine Department, Third Faculty of Medicine Charles University, Division of Cell and Molecular Biology, Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Internal Medicine Department, Vinohrady Teatching Hospital, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
Male, Luminescence, Polymers, Endocrinology, Diabetes and Metabolism, Adipose tissue, Tissue Culture Techniques, 0302 clinical medicine, Endocrinology, Weight loss, Blood plasma, MESH: Obesity, 2. Zero hunger, 0303 health sciences, medicine.diagnostic_test, MESH: Kinetics, MESH: Luminescence, MESH: Molecular Weight, MESH: Waist-Hip Ratio, Biopsy, Needle, MESH: Enzyme-Linked Immunosorbent Assay, General Medicine, MESH: Adiponectin, 3. Good health, MESH: Polymers, Very low calorie diet, Adipose Tissue, Female, Adiponectin, medicine.symptom, MESH: Adipose Tissue, Adult, medicine.medical_specialty, MESH: Biopsy, Needle, food.diet, Blotting, Western, 030209 endocrinology & metabolism, Enzyme-Linked Immunosorbent Assay, Biology, 03 medical and health sciences, MESH: Weight Loss, food, Western blot, Internal medicine, MESH: Body Height, Weight Loss, medicine, Humans, MESH: Blotting, Western, Secretion, Obesity, MESH: Tissue Culture Techniques, 030304 developmental biology, Caloric Restriction, MESH: Caloric Restriction, MESH: Humans, Waist-Hip Ratio, Body Weight, MESH: Adult, medicine.disease, Body Height, MESH: Male, Culture Media, MESH: Body Weight, Molecular Weight, Kinetics, MESH: Culture Media, MESH: Female
Abstract

ObjectiveAdiponectin is a protein abundantly secreted by the adipose tissue (AT). Plasma adiponectin levels are decreased in obese, insulin-resistant, and type 2 diabetic patients. Various multimeric complexes, i.e. high-, middle-, and low-molecular weight isoforms (HMW, MMW and LMW), are present in plasma. Here, we investigated the effect of weight reducing diet on the distribution of adiponectin isoforms in plasma and on their secretion in AT explants from obese subjects.DesignA total of 20 obese subjects (age 37.8±7.3 years, body mass index 33.9±5.0 kg/m2) underwent eight weeks of very low-calorie diet (VLCD). A needle biopsy of subcutaneous abdominal AT and blood samples were taken before and after dietary intervention. AT explants were incubated in culture medium for 4 h. ELISA assay and western blot analyses were used to identify adiponectin complexes in culture media and in plasma.ResultsThe distribution of adiponectin polymers in plasma was different from that secreted in human AT explants. Before VLCD, the relative amount of HMW isoform was 75.5±9.1% of total adiponectin in culture media and 52.2±11.2% in plasma. Despite the diet-induced weight loss and improvement of insulin sensitivity, VLCD neither induced change in total adiponectin level nor in the ratio of HMW to total adiponectin in plasma and in culture media of AT explants.ConclusionsThe profile of adiponectin polymeric isoforms secreted by AT explants into culture media differs from the plasma profile. A dietary intervention leading to weight loss and improvement of insulin sensitivity was not associated with modifications of AT secretion of total or HMW adiponectin.

Published
2009

44. Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition

Author

Louis Casteilla, Philippe Valet, Sandy Bour, Luc Pénicaud, Mari Miiluniemi, Béatrice Cousin, Zsuzsa Iffiú-Soltész, Marko Salmi, Sylvie Caspar-Bauguil, Sirpa Jalkanen, Craig Stolen, Christian Carpéné, Maryse Nibbelink, Développement et Communication Chimique chez les Insectes ( DCCI ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MediCity Research Laboratory and Department of Medical Microbiology, University of Turku-National Public Health Institute, Simon, Marie Francoise, and Delon, Viviane

Subjects
MESH: Semicarbazides, AOC3, Obesity/genetics, Adipose tissue, MESH: Flow Cytometry, White adipose tissue, Inbred C57BL, MESH: Mice, Knockout, Transgenic, Mice, Leukocytes, MESH: Obesity, MESH: Animals, Mice, Knockout, Amine oxidase (copper-containing), food and beverages, Natural killer T cell, Flow Cytometry, Leukocyte extravasation, Semicarbazides, Cell Adhesion Molecules/*deficiency/*genetics, Adipose Tissue, MESH: Cell Adhesion Molecules, Leukocytes/*physiology, Amine Oxidase (Copper-Containing), medicine.symptom, Infiltration (medical), MESH: Adipose Tissue, medicine.medical_specialty, MESH: Mice, Transgenic, Knockout, Mice, Transgenic, Inflammation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Monoamine Oxidase, Pathology and Forensic Medicine, MESH: Leukocytes, Monoamine Oxidase/*deficiency, MESH: Mice, Inbred C57BL, Internal medicine, medicine, Animals, Humans, Obesity, Monoamine Oxidase, MESH: Mice, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Humans, Amine Oxidase (Copper-Containing)/*deficiency/*genetics, medicine.disease, Adipose Tissue/pathology/*physiology, Mice, Inbred C57BL, Endocrinology, Immunology, MESH: Amine Oxidase (Copper-Containing), Semicarbazides/*pharmacology, Cell Adhesion Molecules, Regular Articles
Abstract

1525-2191 (Electronic) Journal Article; Obesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-month-old AOC3-KO males than in age-matched wild-type controls. However, WAT from AOC3-KO mice contained lower CD45 mRNA levels and fewer CD45(+) leukocytes. Subpopulation analyses revealed a diminished infiltration of WAT by T cells, macrophages, natural killer, and natural killer T cells. A decrease in leukocyte content in WAT was also detected in female AOC3-KO mice as early as 2 months of age, whereas increased fat mass was evident by 6 months of age. Reduced CD45(+) populations in WAT of AOC3-KO mice was not rescued by human SSAO/VAP-1 expression on adipocytes under the control of aP2, suggesting the importance of vascular AOC3 in leukocyte entrance into fat. Our results indicate that SSAO/VAP-1 is instrumental for the presence of leukocytes in WAT. Therefore, AOC3-KO mice present a unique model of mild obesity, characterized by increased WAT devoid of low-grade inflammation.

Published
2009

45. Elevated expression of osteopontin may be related to adipose tissue macrophage accumulation and liver steatosis in morbid obesity

Author

Adeline Bertola, Keith N. Frayn, Yannick Le Marchand-Brustel, Joan Tordjman, Moncef Dahman, S. McQuaid, Albert Tran, Philippe Gual, Karine Clément, Vanessa Deveaux, Jean Gugenheim, Pierre-Michel Huet, Rodolphe Anty, Déborah Rousseau, Sophie Lotersztajn, Abdelilah Wakkach, Stéphanie Bonnafous, Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Signalisation moléculaire et obésité, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Transduction du Signal : Signalisation Calcique et Phosphorylation, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford [Oxford], Environnement et Grandes Cultures (EGC), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Service de Chirurgie Digestive et Transplantation Hépatique, Hôpital Archet II, Digestive Center, Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -IFR50-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique, physiopathologie et ingénierie du tissu osseux ( GéPITOS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Oxford Centre for Diabetes, Endocrinology and Metabolism ( OCDEM ), Environnement et Grandes Cultures ( EGC ), AgroParisTech-Institut National de la Recherche Agronomique ( INRA ), Epidémiologie et écologie des maladies animales ( Epidémiologie ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ), CHU Nice, Université Nice Sophia Antipolis (1965 - 2019) (UNS), University of Oxford, and Service de Chirurgie Digestive / Centre de Transplantation Hépatique [CHU Nice]

Subjects
Male, MESH : RNA, Messenger, Endocrinology, Diabetes and Metabolism, Mice, 0302 clinical medicine, MESH : Oleic Acid, MESH: Animals, Osteopontin, MESH : Immunoblotting, MESH : Macrophages, Liver injury, 0303 health sciences, Tumor, MESH: Middle Aged, MESH: Immunoblotting, MESH : Reverse Transcriptase Polymerase Chain Reaction, Obesity, Morbid, Hyaluronan Receptors, Adipose Tissue, Tumor necrosis factor alpha, MESH: Adipose Tissue, medicine.medical_specialty, MESH: Gene Expression, MESH: Antigens, CD44, MESH : Adipose Tissue, 03 medical and health sciences, MESH: Weight Loss, Humans, MESH : Middle Aged, RNA, Messenger, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Humans, Tumor Necrosis Factor-alpha, Macrophages, MESH : Humans, MESH: Oleic Acid, MESH: Adult, medicine.disease, Mice, Inbred C57BL, MESH : Gene Expression, Endocrinology, MESH: Tumor Necrosis Factor-alpha, MESH: Female, MESH: Liver, MESH : Fatty Liver, MESH: Osteopontin, Messenger, Adipose tissue, Gene Expression, Inbred C57BL, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Antigens, CD44, MESH : Female, MESH : Osteopontin, CD44, Morbid, Receptor, MESH: Fatty Liver, MESH : Tumor Necrosis Factor-alpha, biology, Reverse Transcriptase Polymerase Chain Reaction, Fatty liver, MESH : Adult, Middle Aged, Liver, Female, Obesity Studies, Adult, MESH : Obesity, Morbid, MESH: Cell Line, Tumor, MESH : Male, Immunoblotting, 030209 endocrinology & metabolism, MESH : Mice, Inbred C57BL, Cell Line, Insulin resistance, stomatognathic system, MESH: Mice, Inbred C57BL, Cell Line, Tumor, Internal medicine, MESH : Mice, Weight Loss, Internal Medicine, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, Antigens, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, MESH : Cell Line, Tumor, MESH : Liver, MESH: Macrophages, MESH: Obesity, Morbid, MESH: Male, Fatty Liver, biology.protein, RNA, MESH : Animals, MESH : Weight Loss, Steatosis, Oleic Acid
Abstract

OBJECTIVE—Osteopontin (OPN) plays an important role in the development of insulin resistance and liver complications in dietary murine models. We aimed to determine the expression pattern of OPN and its receptor CD44 in obese patients and mice according to insulin resistance and liver steatosis. RESEARCH DESIGN AND METHODS—OPN and CD44 expressions were studied in 52 morbidly obese patients and in mice. Cellular studies were performed in HepG2 cells. RESULTS—Hepatic OPN and CD44 expressions were strongly correlated with liver steatosis and insulin resistance in obese patients and mice. This increased OPN expression could be due to the accumulation of triglycerides, since fat loading in HepG2 promotes OPN expression. In contrast, OPN expression in adipose tissue (AT) was enhanced independently of insulin resistance and hepatic steatosis in obese patients. The elevated OPN expression in AT was paralleled with the AT macrophage infiltration, and both phenomena were reversed after weight loss. The circulating OPN level was slightly elevated in obese patients and was not related to liver steatosis. Further, AT did not appear to secrete OPN. In contrast, bariatric surgery–induced weight loss induced a strong increase in circulating OPN. CONCLUSIONS—The modestly elevated circulating OPN levels in morbidly obese patients were not related to liver steatosis and did not appear to result from adipose tissue secretion. In subcutaneous AT, expression of OPN was directly related to macrophage accumulation independently from liver complications. In contrast, hepatic OPN and CD44 expressions were related to insulin resistance and steatosis, suggesting their local implication in the progression of liver injury.

Published
2009

46. Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women

Author

Claus Holst, Nathalie Vega, Moira A. Taylor, J. Alfredo Martínez, Eva Klimcakova, Thorkild I. A. Sørensen, Dominique Langin, Sébastien Déjean, Jean M. Oppert, Peter Arner, Hubert Vidal, Nathalie Viguerie, Karine Clément, Frédéric Capel, Wim H. M. Saris, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche sur les obésités, CHU Toulouse [Toulouse]-Laboratoire, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Lyon-Sud, FACULTE DE LYON, Centre de Recherche en Nutrition Humaine, Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Midicine Karolinska Institute, Karolinska University Hospital Huddinge, Department of Sports Medicine of Charles University, Faculty of Medicine Charles University, Department of Physiology and nutrition University of Navarra, Universidad de Navarra [Pamplona] (UNAV), Department of Human Biology Nutrition and Toxicology Research Institute, Maastricht University [Maastricht], The Netherlands Institute of Preventive Medicine, Institute of Preventive Medicine, School of Biomedical Sciences Queen's Medical Center, University of Nottingham Medical School, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse, Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Nutrition and Endocrinology AP / HP, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR 31 Louis Bugnard ( IFR 31 ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Institut de Mathématiques de Toulouse UMR5219 ( IMT ), Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-PRES Université de Toulouse-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Universidad de Navarra [Pamplona] ( UNAV ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Humane Biologie, RS: NUTRIM - R1 - Metabolic Syndrome, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Transcription, Genetic, Endocrinology, Diabetes and Metabolism, MESH: Energy Intake, Biochemistry, Body Mass Index, 0302 clinical medicine, Endocrinology, Gene expression, MESH: Genetic Variation, MESH : Adaptor Proteins, Signal Transducing, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Addipose tissue, Reducing, MESH: Mitochondrial Proteins, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, Adipose Tissue, Body Composition, MESH: Adipose Tissue, medicine.medical_specialty, Diet, Reducing, MESH : Body Composition, MESH : Adipose Tissue, MESH: Body Mass Index, MESH : Receptors, Glucocorticoid, 03 medical and health sciences, MESH: Weight Loss, Genetic, Humans, MESH : Fatty Acid-Binding Proteins, MESH : Mitochondrial Proteins, MESH: Adaptor Proteins, Signal Transducing, MESH: Humans, MESH : Humans, Signal Transducing, Genetic Variation, MESH: Adult, Autophagy-Related Protein 8 Family, MESH: Body Composition, medicine.disease, Obesity, MESH : Energy Metabolism, MESH : Body Mass Index, Energy intake, Body mass index, MESH: Female, Candidate gene, MESH: Receptors, Glucocorticoid, Clinical Biochemistry, Adipose tissue, Blood lipids, Glucocorticoid, Weight loss, Sirtuin 3, Receptors, MESH : RNA, Sirtuins, MESH: Obesity, MESH : Female, Nutrición y dietética [Ciencias de la Salud], MESH : Diet, Reducing, 2. Zero hunger, MESH : Sirtuins, MESH: Diet, Reducing, Microfilament Proteins, MESH: Energy Metabolism, Adaptor Proteins, MESH : Adult, MESH: Sirtuins, MESH : Obesity, Female, medicine.symptom, Transcription, Adult, MESH : Microfilament Proteins, 030209 endocrinology & metabolism, Context (language use), Biology, Fatty Acid-Binding Proteins, MESH: Fatty Acid-Binding Proteins, Mitochondrial Proteins, MESH: Microfilament Proteins, Receptors, Glucocorticoid, MESH : Genetic Variation, MESH: RNA, Internal medicine, Weight Loss, medicine, 030304 developmental biology, Adaptor Proteins, Signal Transducing, MESH: Transcription, Genetic, Biochemistry (medical), MESH : Transcription, Genetic, MESH : Energy Intake, Diet, MESH: Oligonucleotide Array Sequence Analysis, RNA, MESH : Weight Loss, Energy Intake, Energy Metabolism
Abstract

Context: Hypoenergetic diets are used to reduce body fat mass and metabolic risk factors in obese subjects. The molecular changes in adipose tissue associated with weight loss and specifically related to the dietary composition are poorly understood. Objective: We investigated adipose tissue gene expression from human obese women according to energy deficit and, the fat and carbohydrate content of the diet. Design & setting: Obese subjects recruited among 8 European clinical centers followed 10 weeks of either a low fat (high carbohydrate) or a moderate fat (low carbohydrate) hypoenergetic diet. Subjects: Two sets of 47 women in each dietary arm were selected among 648 subjects matched for anthropometric and biological parameters. Main Outcome Measure: We measured adipose tissue gene expression changes in one set using a candidate gene approach. The other set was used to survey 24469 transcripts using DNA microarrays. Results were analyzed using dedicated statistical methods. Diet-sensitive regulations were confirmed on the other set of subjects. Results: The two diets induced similar weight loss and similar changes for most of the biological variables except for components of the blood lipid profile. A thousand genes were regulated by energy restriction. We validated an effect of the fat-to-carbohydrate ratio for five genes (FABP4, NR3C1, SIRT3, FNTA and GABARAPL2) with increased expression during the moderate fat diet. Conclusions: Energy restriction had a more pronounced impact on variations in human adipose tissue gene expression than macronutrient composition. The macronutrient-sensitive regulation of a subset of genes may influence adipose tissue function and metabolic response. AD - INSERM, U858, Laboratoire de Recherches sur les Obesites, Institut de Medecine Moleculaire de Rangueil, Toulouse; Universite Paul Sabatier, Institut Louis Bugnard IFR31, Toulouse; Centre Hospitalier Universitaire de Toulouse, France; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; INSERM, UMR -870; INRA U-1235; Faculte de Medecine Lyon-Sud universite de Lyon 1; Centre de Recherche en Nutrition Humaine, Hospices civils de Lyon; Lyon, France; Institut de Mathematiques de Toulouse UMR 5219, Universite Paul-Sabatier, Toulouse, France; Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Sports Medicine, Centre of Preventive Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain; Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands; Institute of Preventive Medicine, Centre for Health and Society, Copenhagen University Hospital, Copenhagen, Denmark; School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham Medical School, Nottingham, United Kingdom; INSERM, Nutriomique U872 (Team 7), 75004 Paris, France; Universites Pierre et Marie Curie-Paris6, UMR-S 872, Cordelier Research Center & Paris Descartes, 75006 Paris; and Assistance Publique/Hopitaux de Paris (AP-HP), Pitie Salpetriere Hospital, Nutrition and Endocrinology department, 75013 Paris, France.

Published
2008

47. Impact of visceral adipose tissue on liver metabolism and insulin resistance. Part II: Visceral adipose tissue production and liver metabolism

Author

J. Girard, Max Lafontan, Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Simon, Marie Francoise, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH : Fatty Liver, Endocrinology, Diabetes and Metabolism, Adipose tissue, White adipose tissue, MESH : Hepatocytes, MESH: Hepatocytes, chemistry.chemical_compound, Endocrinology, MESH : Diabetes Mellitus, Type 2, Nonalcoholic fatty liver disease, MESH : Cardiovascular Diseases, MESH: Fatty Liver, MESH : Viscera, Fatty liver, General Medicine, MESH : Triglycerides, MESH: Viscera, MESH: Glucose, MESH: Insulin Resistance, Adipose Tissue, Liver, Cardiovascular Diseases, MESH : Insulin Resistance, MESH: Adipose Tissue, MESH: Diabetes Mellitus, Type 2, MESH: Triglycerides, medicine.medical_specialty, Adipose tissue macrophages, Biology, Carbohydrate metabolism, MESH : Adipose Tissue, Insulin resistance, Internal medicine, Internal Medicine, medicine, Humans, Triglycerides, MESH: Humans, Triglyceride, MESH : Glucose, MESH : Humans, MESH: Cardiovascular Diseases, MESH : Liver, medicine.disease, Fatty Liver, Viscera, Glucose, Diabetes Mellitus, Type 2, chemistry, Hepatocytes, Insulin Resistance, MESH: Liver
Abstract

International audience; Excess visceral adipose tissue is associated with anomalies of blood glucose homoeostasis, elevation of plasma triglycerides and low levels of high-density lipoprotein cholesterol that contribute to the development of type-2 diabetes and cardiovascular syndromes. Visceral adipose tissue releases a large amount of free fatty acids and hormones/cytokines in the portal vein that are delivered to the liver. The secreted products interact with hepatocytes and various immune cells in the liver. Altered liver metabolism and determinants of insulin resistance associated with visceral adipose tissue distribution are discussed, as well as, determinants of an insulin-resistant state promoted by the increased free fatty acids and cytokines delivered by visceral adipose tissue to the liver.

Published
2008

48. Stathmin-like 2, a developmentally-associated neuronal marker, is expressed and modulated during osteogenesis of human mesenchymal stem cells

Author

Marcel Scheideler, Christian Dani, Gabriele Grenningloh, Chiara Chiellini, Gérard Ailhaud, Olivia Cochet, Ez-Zoubir Amri, Zlatko Trajanoski, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Center for Psychiatric Neuroscience, Lausanne, Université de Lausanne (UNIL), Institute for Genomics and Bioinformatics, Graz, and Karl-Franzens-Universität [Graz, Autriche]

Subjects
RHOA, Pyridines, MESH: Neurons, Golgi Apparatus, Biochemistry, Dexamethasone, chemistry.chemical_compound, Cytosol, 0302 clinical medicine, MESH: Cytosol, Osteogenesis, Adipocyte, Adipocytes, MESH: Protein Kinase Inhibitors, MESH: Osteogenesis, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Stem cell transplantation for articular cartilage repair, Neurons, rho-Associated Kinases, 0303 health sciences, Adipogenesis, biology, MESH: Bone Marrow Cells, Osteoblast, MESH: Amides, Cell biology, medicine.anatomical_structure, Adipose Tissue, MESH: Dexamethasone, MESH: Membrane Proteins, Stem cell, MESH: rho-Associated Kinases, MESH: Adipose Tissue, medicine.medical_specialty, Biophysics, Bone Marrow Cells, Stathmin, 03 medical and health sciences, MESH: Golgi Apparatus, Internal medicine, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Protein Kinase Inhibitors, Molecular Biology, MESH: Adipocytes, 030304 developmental biology, MESH: RNA, Messenger, MESH: Osteoblasts, Osteoblasts, MESH: Humans, Mesenchymal stem cell, MESH: Pyridines, MESH: Biological Markers, Membrane Proteins, Mesenchymal Stem Cells, Cell Biology, Amides, Endocrinology, MESH: Mesenchymal Stem Cells, chemistry, biology.protein, MESH: Adipogenesis, Biomarkers, 030217 neurology & neurosurgery
Abstract

International audience; Stathmin-like 2 (STMN2) protein, a neuronal protein of the stathmin family, has been implicated in the microtubule regulatory network as a crucial element of cytoskeletal regulation. Herein, we describe that STMN2 expression increases at both mRNA and protein levels during osteogenesis of human mesenchymal stem cells derived from adipose tissue (hMADS cells) and bone marrow (hBMS cells), whereas it decreases to undetectable levels during adipogenesis. STMN2 protein is localized in both Golgi and cytosolic compartments. Its expression appears modulated in osteoblasts by nerve growth factor, dexamethasone or RhoA kinase inhibitor Y-27632 which are known effectors of osteogenesis. Thus STMN2 appears a novel marker of osteogenesis and osteoblast per se, that could play a role in the regulation of the adipocyte/osteoblast balance.

Published
2008

49. Variations in DNA elucidate molecular networks that cause disease

Author

Aldons J. Lusis, Susanna Wang, Lawrence W. Castellini, Solveig K. Sieberts, Bin Zhang, Sudheer Doss, Anatole Ghazalpour, Chunsheng Zhang, Marie-France Champy, Steve Horvath, Valur Emilsson, Amy Leonardson, Pek Yee Lum, Jun Zhu, John Lamb, Stephen W. Edwards, Xia Yang, Shirly Pinto, Yanqing Chen, Douglas J. MacNeil, Thomas A. Drake, Eric E. Schadt, Cryogenics Laboratory (CRYOGENICS LABORATORY), Huazhong University of Science and Technology [Wuhan] (HUST)-Wuhan University [China], Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Candidate gene, MESH: Chromosomes, Mammalian, Gene regulatory network, Linkage Disequilibrium, MESH: Variation (Genetics), Mice, 0302 clinical medicine, MESH: Metabolic Syndrome X, Phosphoprotein Phosphatases, MESH: Obesity, MESH: Animals, Gene Regulatory Networks, MESH: Gene Regulatory Networks, Genetics, Metabolic Syndrome, 0303 health sciences, education.field_of_study, Multidisciplinary, MESH: Apolipoprotein A-II, MESH: Genetic Predisposition to Disease, MESH: Ribosomal Proteins, MESH: Reproducibility of Results, Phenotype, MESH: Linkage Disequilibrium, Adipose Tissue, Liver, Female, MESH: Membrane Proteins, Functional genomics, MESH: Adipose Tissue, Apolipoprotein A-II, MESH: Lipoprotein Lipase, Ribosomal Proteins, Population, Quantitative Trait Loci, Genomics, Quantitative trait locus, Biology, MESH: Phenotype, Article, 03 medical and health sciences, MESH: Phosphoprotein Phosphatases, Animals, Genetic Predisposition to Disease, Obesity, education, Gene, MESH: Mice, 030304 developmental biology, Macrophages, MESH: Macrophages, Genetic Variation, Membrane Proteins, Reproducibility of Results, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Chromosomes, Mammalian, Forward genetics, MESH: Male, MESH: Quantitative Trait Loci, Lipoprotein Lipase, MESH: Lod Score, Lod Score, MESH: Female, 030217 neurology & neurosurgery, MESH: Liver
Abstract

Identifying variations in DNA that increase susceptibility to disease is one of the primary aims of genetic studies using a forward genetics approach. However, identification of disease-susceptibility genes by means of such studies provides limited functional information on how genes lead to disease. In fact, in most cases there is an absence of functional information altogether, preventing a definitive identification of the susceptibility gene or genes. Here we develop an alternative to the classic forward genetics approach for dissecting complex disease traits where, instead of identifying susceptibility genes directly affected by variations in DNA, we identify gene networks that are perturbed by susceptibility loci and that in turn lead to disease. Application of this method to liver and adipose gene expression data generated from a segregating mouse population results in the identification of a macrophage-enriched network supported as having a causal relationship with disease traits associated with metabolic syndrome. Three genes in this network, lipoprotein lipase (Lpl), lactamase β (Lactb) and protein phosphatase 1-like (Ppm1l), are validated as previously unknown obesity genes, strengthening the association between this network and metabolic disease traits. Our analysis provides direct experimental support that complex traits such as obesity are emergent properties of molecular networks that are modulated by complex genetic loci and environmental factors. Complex human diseases result from the interplay of many genetic and environmental factors. To build up a picture of the factors contributing to one such disease, obesity, gene expression was evaluated as a quantitative trait in blood and adipose tissue samples from hundreds of Icelandic subjects aged 18 to 85. The results reveal a tendency to certain characteristic patterns of gene activation in the fatty tissues — though to a much lesser extent in the blood — of people with a higher body mass index. A transcriptional network constructed from the adipose tissue data has significant overlap with a network based on mouse adipose tissue data. Experimental support for the idea that complex diseases are emergent properties of molecular networks influenced by genes and environment comes from a study in mice. Mice were examined for disturbances in genetic expression networks that correlate with metabolic traits associated with obesity, diabetes and atherosclerosis. Three genes — Lpl, Lactb and Ppm1l — were identified as previously unknown obesity genes. This 'molecular network' approach raises the prospect that therapies might be directed at whole 'disease networks', rather than at one or two specific genes. Standard approaches to identify the genetic changes that lead to disease are reversed by examination of genetic networks for perturbations that are associated with disease states, and following up candidate genes from there. This begins with three genes in mice that lead to obesity when mutated, demonstrating that complex genetic–environmental traits can be dissected with this new approach.

Published
2008

50. Restoration of body energy reserves during refeeding in rats is dependent on both the intensity of energy restriction and the metabolic status at the onset of starvation

Author

Robin, Jean-Patrice, Decrock, Frédéric, Herzberg, Gene, Mioskowski, Eliane, Le Maho, Yvon, Bach, André, Groscolas, René, Gaillard, Brigitte, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Biochemistry Department, Memorial University, and Memorial University - St John's

Subjects
MESH: Caloric Restriction, MESH: Fatty Acids, Nonesterified, MESH: Rats, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH: Energy Metabolism, starvation, MESH: Starvation, MESH: Rats, Wistar, MESH: Energy Intake, MESH: Nutritional Status, MESH: Male, lipids, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, MESH: 3-Hydroxybutyric Acid, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH: Animals, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, MESH: Adipose Tissue, MESH: Food, MESH: Lipid Metabolism, energy
Abstract

During starvation, after a short dynamic period of adaptation (phase I), a metabolic steady state is reached in which proteins are spared and lipids provide most of the energy expended [phase II (P2)]. However, protein breakdown increases dramatically once a lower threshold of body lipids is reached [phase III (P3)]. Body composition, energy intake, energy expenditure, and energy efficiency were determined in 8 groups of rats (fed, food-deprived up to P2 or P3 of starvation and refed for 3 d, 7 d, or until body mass restoration) to determine whether the kinetics of lipid and/or protein reserve recovery may be slowed down when refeeding occurs after the lipid threshold has been reached. Despite larger losses, P3 refed rats restored their body reserves as efficiently as those refed in P2. Whatever the nutritional status at the onset of refeeding, rehydration occurred first and hyperphagia played a more important role than hypometabolism in the restoration of the lost reserves. However, the pattern of body component gains was different during early refeeding. In P3 refed rats, body lipids were restored preferentially by significant contribution from endogenous lipid production. Thus, the extent of lipid depletion has important consequences for the restoration pattern of the body reserves. It depends not only on the intensity of the energy restriction (partial or total) as already demonstrated but also on the metabolic status at the onset of refeeding. These results may have significant implications on the way refeeding should be conducted after severe energy depletion.

Published
2008

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