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157 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. SHP2 drives inflammation-triggered insulin resistance by reshaping tissue macrophage populations

Author

Ophélie Pereira, Jean Personnaz, Céline Saint-Laurent, Toshiyuki Araki, Maithé Tauber, Jean-Pierre Salles, Philippe Valet, Adélaïde Gélineau, Mickaël Canouil, Romain Paccoud, Armelle Yart, Jacques Weill, Jean-Philippe Pradere, Mylène Tajan, Cédric Dray, Enzo Piccolo, Sophie Le Gonidec, Inès Baba, Thomas Edouard, Emmanuel L. Gautier, Haoussa Askia, Philippe Froguel, Benjamin G. Neel, Nicolas Beton, Simon Deleruyelle, Johanna Auriau, Sophie Branka, Alizée Dortignac, Maxime Branchereau, Isabelle Castan, Christophe Heymes, Rémy Burcelin, Julie Charpentier, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - 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), Geroscience and rejuvenation research center (RESTORE), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-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), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (CPTP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), ANR-17-CE14-0016,HOLISTic,Rôle de la protéine HMGB1 au cours du stress metabolique(2017), ANR-17-CE14-0009,CAPTOR,Contrôler la fonction des progéniteurs du tissu adipeux pour améliorer les désordres métaboliques de l'obésité(2017), and ANR-17-CE14-0023,TARGETKC,Homéostasie et rôles des cellules de Kupffer dans la stéatohépatite(2017)

Subjects
MESH: Inflammation, medicine.medical_specialty, endocrine system diseases, education, Inflammation, Type 2 diabetes, MESH: Mice, Knockout, Diabetes Mellitus, Experimental, Proinflammatory cytokine, Mice, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, MESH: Diabetes Mellitus, Experimental, medicine, Animals, Humans, Glucose homeostasis, MESH: Animals, Macrophage homeostasis, MESH: Mice, 030304 developmental biology, Mice, Knockout, 0303 health sciences, MESH: Humans, business.industry, Macrophages, Monocyte, nutritional and metabolic diseases, MESH: Macrophages, General Medicine, medicine.disease, 3. Good health, MESH: Insulin Resistance, medicine.anatomical_structure, Endocrinology, Adipose Tissue, Diabetes Mellitus, Type 2, Lipotoxicity, Insulin Resistance, medicine.symptom, business, MESH: Adipose Tissue, 030217 neurology & neurosurgery, MESH: Diabetes Mellitus, Type 2
Abstract

Insulin resistance is a key event in type 2 diabetes onset and a major comorbidity of obesity. It results from a combination of fat excess-triggered defects, including lipotoxicity and metaflammation, but the causal mechanisms remain difficult to identify. Here, we report that hyperactivation of the tyrosine phosphatase SHP2 found in Noonan syndrome (NS) led to an unsuspected insulin resistance profile uncoupled from altered lipid management (for example, obesity or ectopic lipid deposits) in both patients and mice. Functional exploration of an NS mouse model revealed this insulin resistance phenotype correlated with constitutive inflammation of tissues involved in the regulation of glucose metabolism. Bone marrow transplantation and macrophage depletion improved glucose homeostasis and decreased metaflammation in the mice, highlighting a key role of macrophages. In-depth analysis of bone marrow-derived macrophages in vitro and liver macrophages showed that hyperactive SHP2 promoted a proinflammatory phenotype, modified resident macrophage homeostasis, and triggered monocyte infiltration. Consistent with a role of SHP2 in promoting inflammation-driven insulin resistance, pharmaceutical SHP2 inhibition in obese diabetic mice improved insulin sensitivity even better than conventional antidiabetic molecules by specifically reducing metaflammation and alleviating macrophage activation. Together, these results reveal that SHP2 hyperactivation leads to inflammation-triggered metabolic impairments and highlight the therapeutical potential of SHP2 inhibition to ameliorate insulin resistance.

Published
2021

4. 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

5. 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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6. Autophagy inhibition blunts PDGFRA adipose progenitors' cell-autonomous fibrogenic response to high-fat diet

Author

Nadine Suffee, Geneviève Marcelin, Emmanuel L. Gautier, Amélie Lacombe, Carla Da Cunha, Isabelle Dugail, Christine Rouault, Nataliya Sokolovska, Karine Clément, Arnaud Leclerc, Camille Gamblin, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dugail, Isabelle, Instituts Hospitalo-Universitaires - Institut de Cardiologie-Métabolisme-Nutrition - - ICAN2010 - ANR-10-IAHU-0005 - IAHU - VALID, Appel à projets générique - LIPA, une nouvelle cible thérapeutique pour le traitement des maladies cardiométaboliques - - LIPOCAMD2014 - ANR-14-CE12-0017 - Appel à projets générique - VALID, Contrôler la fonction des progéniteurs du tissu adipeux pour améliorer les désordres métaboliques de l'obésité - - CAPTOR2017 - ANR-17-CE14-0009 - AAPG2017 - VALID, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Sorbonne Université (SU), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], Funding from the French National Agency of Research (ANR) is acknowledged and includes support from RHU collaborative grant CARMMA [15-RHUS-0003], from the Institute of Cardiometabolism and Nutrition (reference ANR-10-IAHU-05, to AL), ANR-14-CE12-0017-01 LIPOCAMD and ANR CAPTOR (ANR-17-CE14-0009). GM 615 and KC also received funds from AFERO, EFSD-Novo Nordisk, and SFD to support for salaries and consumables., ANR-10-IAHU-0005,ICAN,Institut de Cardiologie-Métabolisme-Nutrition(2010), ANR-14-CE12-0017,LIPOCAMD,LIPA, une nouvelle cible thérapeutique pour le traitement des maladies cardiométaboliques(2014), ANR-17-CE14-0009,CAPTOR,Contrôler la fonction des progéniteurs du tissu adipeux pour améliorer les désordres métaboliques de l'obésité(2017), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de nutrition [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP]

Subjects
0301 basic medicine, collagen, MESH: Signal Transduction, Male, obesity, Receptor, Platelet-Derived Growth Factor alpha, [SDV.BA] Life Sciences [q-bio]/Animal biology, MESH: Bone Morphogenetic Proteins, MESH: Receptor, Platelet-Derived Growth Factor alpha, [SDV]Life Sciences [q-bio], Adipose tissue, Muscle Proteins, Autophagy-Related Protein 7, Extracellular matrix, chloroquine, chemistry.chemical_compound, Adipose Tissue, Brown, Fibrosis, Transforming Growth Factor beta, Adipocyte, ScAT: subcutaneous adipose tissue, MESH: Animals, OvAT: ovarian adipose tissue, Promoter Regions, Genetic, Sex Characteristics, [SDV.BA]Life Sciences [q-bio]/Animal biology, Stem Cells, Cell biology, Extracellular Matrix, KO: knockout, Adipose Tissue, Adipogenesis, MESH: Fibrosis, Bone Morphogenetic Proteins, HFD: high-fat diet, Female, ATG7, MESH: Adipose Tissue, MESH: Sex Characteristics, Signal Transduction, Research Paper, subcutaneous adipose tissue, TGF-BMP: transforming growth factor-bone morphogenic protein ARTICLE HISTORY KEYWORDS ATG7, MESH: Trans-Activators, MESH: Stem Cells, Biology, MESH: Extracellular Matrix, Diet, High-Fat, ECM: extracellular matrix, MESH: Adipose Tissue, Brown, 03 medical and health sciences, Paracrine signalling, MESH: Muscle Proteins, EpiAT: epididymal adipose tissue, MESH: Mice, Inbred C57BL, MESH: Promoter Regions, Genetic, medicine, Autophagy, MESH: Autophagy, Animals, Abbreviations: CQ: chloroquine, Heart Atria, Progenitor cell, Molecular Biology, MESH: Transforming Growth Factor beta, 030102 biochemistry & molecular biology, GTF2IRD1: 25 general transcription factor II I repeat domain-containing 1, MESH: Autophagy-Related Protein 7, Cell Biology, medicine.disease, MESH: Male, Mice, Inbred C57BL, MESH: Diet, High-Fat, MicroRNAs, 030104 developmental biology, chemistry, PDGFR: platelet derived growth factor receptor, Trans-Activators, MESH: Heart Atria, MESH: Female, MESH: MicroRNAs
Abstract

International audience; Adipose tissue (AT) fibrosis in obesity compromises adipocyte functions and responses to intervention-induced weight loss. It is driven by AT progenitors with dual fibro/adipogenic potential, but pro-fibrogenic pathways activated in obesity remain to be deciphered. To investigate the role of macroautophagy/autophagy in AT fibrogenesis, we used Pdgfra-CreErt2 transgenic mice to create conditional deletion of Atg7 alleles in AT progenitor cells (atg7 cKO) and examined sex-dependent, depot-specific AT remodeling in high-fat diet (HFD)-fed mice. Mice with atg7 cKO had markedly decreased extracellular matrix (ECM) gene expression in visceral, subcutaneous, and epicardial adipose depots compared to Atg7lox/lox littermates. ECM gene program regulation by autophagy inhibition occurred independently of changes in the mass of fat tissues or adipocyte numbers of specific depots, and cultured preadipocytes treated with pharmacological or siRNA-mediated autophagy disruptors could mimic these effects. We found that autophagy inhibition promotes global cell-autonomous remodeling of the paracrine TGF-BMP family landscape, whereas ECM gene modulation was independent of the autophagic regulation of GTF2IRD1. The progenitor-specific mouse model of ATG7 inhibition confirms the requirement of autophagy for white/beige adipocyte turnover, and combined to in vitro experiments, reveal progenitor autophagy dependence for AT fibrogenic response to HFD, through the paracrine remodeling of TGF-BMP factors balance. Abbreviations: CQ: chloroquine; ECM: extracellular matrix; EpiAT: epididymal adipose tissue; GTF2IRD1: general transcription factor II I repeat domain-containing 1; HFD: high-fat diet; KO: knockout; OvAT: ovarian adipose tissue; PDGFR: platelet derived growth factor receptor; ScAT: subcutaneous adipose tissue; TGF-BMP: transforming growth factor-bone morphogenic protein.

Published
2020

7. 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

8. 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

9. 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

10. 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

11. Beneficial role of adipose-derived mesenchymal stem cells from microfragmented fat in a murine model of duchenne muscular dystrophy

Author

Pierre Rocheteau, Mikael Hivelin, Carlo Ferdinando Maria Tremolada, Fabrice Chrétien, David Hardy, Adrien Bouglé, David Briand, Franck Verdonk, Sorbonne Université (SU), Neuropathologie expérimentale - Experimental neuropathology, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 (UPD5), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Italian Image Institute (Milan), Service de Chirurgie plastique, reconstructrice et esthétique [Pompidou], 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 - Paris 5 (UPD5), 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), This work was supported by Région Ile de France, Fondation pour les Gueules Cassées, Fondation Deniker, Agence Nationale de la Recherche (ANR 11BSV202552), and the Institut Pasteur., We thank Grégory Jouvion, DVM, PhD, Dipl. ECVP, for histology interpretation and the Imagopole (PFID) facility of Institut Pasteur., Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Necrosis, Physiology, Duchenne muscular dystrophy, [SDV]Life Sciences [q-bio], Adipose tissue, 030105 genetics & heredity, Dystrophin, 0302 clinical medicine, Fibrosis, MESH: Animals, [SDV.BDD]Life Sciences [q-bio]/Development Biology, MESH: Muscle, Skeletal, adipose-derived mesenchymal stem cells, MESH: Muscle Strength, [SDV.BA]Life Sciences [q-bio]/Animal biology, Phenotype, Adipose Tissue, medicine.symptom, Stem cell, MESH: Adipose Tissue, musculoskeletal diseases, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Proinflammatory cytokine, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Dystrophin, stem cells, MESH: Mice, Inbred C57BL, Physiology (medical), Internal medicine, medicine, MESH: Muscular Dystrophy, Duchenne, Animals, Muscle Strength, microfragmented fat, Muscle, Skeletal, business.industry, Mesenchymal stem cell, Mesenchymal Stem Cells, medicine.disease, Mice, Inbred C57BL, Muscular Dystrophy, Duchenne, Disease Models, Animal, Endocrinology, MESH: Mesenchymal Stem Cells, Neurology (clinical), MESH: Disease Models, Animal, business, 030217 neurology & neurosurgery
Abstract

International audience; Introduction: No etiologic therapy is available for Duchenne muscular dystrophy (DMD), but mesenchymal stem cells were shown to be effective in preclinical models of DMD. The objective of this study is to investigate the effect of microfragmented fat extracted on a murine model of DMD.Methods: Fat tissue was extracted from healthy human participants and injected IM into DMD mice. Histological analysis, cytokines, and force measurement were performed up to 4 weeks after injection.Results: Duchenne muscular dystrophy mice injected with microfragmented fat exhibited an improved muscle phenotype (decreased necrosis and fibrosis), a decrease of inflammatory cytokines, and increased strength.Discussion: Administration of microfragmented fat in key muscles may improve muscular phenotype in patients with DMD.

Published
2018

12. 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

13. Immune Cell Toll-like Receptor 4 Mediates the Development of Obesity- and Endotoxemia-Associated Adipose Tissue Fibrosis

Author

Jacques Grober, Vladimir Stich, Philippe Gui, Corinne Lefort, Geneviève Tavernier, Virginie Bourlier, Isabelle K. Vila, Lenka Rossmeislová, Lucile Mir, Katie Louche, Anne Bouloumié, Nathalie Viguerie, Pierre Marie Badin, Balbine Roussel, Alexia Zakaroff-Girard, Dominique Langin, Cedric Moro, Marie Adeline Marques, Laurent Monbrun, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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, Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), PHOTONIQUE (XLIM-PHOTONIQUE), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Forschungsinstitut für Rationalisierung e.V. (FIR) an der RWTH Aachen, Franco-czech Laboratory for clinical research on obesity, 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), I.K.V. was supported by fellowships from Inserm and Région Midi-Pyrénées. This work was supported by grants from Agence Nationale de la Recherche (LIPOB and OBELIP projects), Région Midi-Pyrénées, Fondation pour la Recherche Médicale, and the Commission of the European Communities (projects DIABAT, HEPADIP, and ADAPT) (to D.L.) and by a grant from Société Francophone du Diabète (to C.M.)., Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Departament Geodinàmica i Geofísica, Facultat de Geologia, Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Charles University [Prague], Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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 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 ), PHOTONIQUE ( XLIM-PHOTONIQUE ), XLIM ( XLIM ), Université de Limoges ( UNILIM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Limoges ( UNILIM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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 ), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), U858 Institut de médecine moléculaire de Rangueil (I2MR), and Institut National de la Santé et de la Recherche Médicale

Subjects
Lipopolysaccharides, MESH: Signal Transduction, MESH: Inflammation, MESH : Toll-Like Receptor 4, Adipose tissue, MESH : Adipocytes, MESH : Lipopolysaccharides, Mice, chemistry.chemical_compound, Fibrosis, Adipocyte, Adipocytes, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Obesity, MESH: Animals, lcsh:QH301-705.5, Mice, Inbred C3H, Toll-like receptor, MESH : Diet, High-Fat, MESH: Toll-Like Receptor 4, 3. Good health, MESH: Insulin Resistance, Adipose Tissue, MESH: Fibrosis, MESH : Fibrosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Obesity, MESH : Insulin Resistance, MESH: Adipose Tissue, Signal Transduction, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adipose tissue macrophages, Biology, Diet, High-Fat, MESH : Adipose Tissue, General Biochemistry, Genetics and Molecular Biology, Immune system, MESH : Mice, Inbred C3H, Internal medicine, MESH : Mice, medicine, Animals, Humans, Obesity, MESH: Mice, Inbred C3H, MESH: Mice, MESH: Adipocytes, Inflammation, MESH : Signal Transduction, MESH : Inflammation, MESH: Humans, MESH : Endotoxemia, MESH : Humans, 3T3-L1, medicine.disease, MESH : Disease Models, Animal, Endotoxemia, Toll-Like Receptor 4, Disease Models, Animal, MESH: Diet, High-Fat, Endocrinology, lcsh:Biology (General), chemistry, MESH: Endotoxemia, MESH : Animals, Insulin Resistance, MESH: Disease Models, Animal, MESH: Lipopolysaccharides, Adipocyte hypertrophy
Abstract

International audience; Adipose tissue fibrosis development blocks adipocyte hypertrophy and favors ectopic lipid accumulation. Here, we show that adipose tissue fibrosis is associated with obesity and insulin resistance in humans and mice. Kinetic studies in C3H mice fed a high-fat diet show activation of macrophages and progression of fibrosis along with adipocyte metabolic dysfunction and death. Adipose tissue fibrosis is attenuated by macrophage depletion. Impairment of Toll-like receptor 4 signaling protects mice from obesity-induced fibrosis. The presence of a functional Toll-like receptor 4 on adipose tissue hematopoietic cells is necessary for the initiation of adipose tissue fibrosis. Continuous low-dose infusion of the Toll-like receptor 4 ligand, lipopolysaccharide, promotes adipose tissue fibrosis. Ex vivo, lipopolysaccharide-mediated induction of fibrosis is prevented by antibodies against the profibrotic factor TGFβ1. Together, these results indicate that obesity and endotoxemia favor the development of adipose tissue fibrosis, a condition associated with insulin resistance, through immune cell Toll-like receptor 4.

Published
2014

14. Body composition in 98 patients awaiting kidney transplantation

Author

A. Desseix, Philippe Chauveau, Rodolphe Thiébaut, Delphine Morel, Thomas Bachelet, Christine Germain, Pierre Merville, Nicole Barthe, Lionel Couzi, Karine Moreau, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine nucléaire [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Statistics In System biology and Translational Medicine (SISTM), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), and AURAD Aquitaine

Subjects
Male, Longitudinal study, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Body Mass Index, MESH: Kidney Transplantation, Absorptiometry, Photon, 0302 clinical medicine, Reference Values, MESH: Postoperative Period, Longitudinal Studies, Postoperative Period, Prospective Studies, MESH: Longitudinal Studies, Kidney transplantation, MESH: Aged, 2. Zero hunger, MESH: Middle Aged, Nutrition and Dietetics, MESH: Reference Values, Nutritional status, Middle Aged, MESH: Nutrition Assessment, MESH: Nutritional Status, MESH: Case-Control Studies, 3. Good health, Adipose Tissue, MESH: Waiting Lists, Preoperative Period, Body Composition, Female, France, MESH: Cholesterol, HDL, MESH: Adipose Tissue, MESH: Cholesterol, LDL, Adult, MESH: Triglycerides, medicine.medical_specialty, Waiting Lists, Nutritional Status, MESH: Absorptiometry, Photon, MESH: Preoperative Period, MESH: Body Mass Index, Fat mass, 03 medical and health sciences, Fat free mass, Internal medicine, medicine, Humans, In patient, Triglycerides, Aged, MESH: Humans, business.industry, Cholesterol, HDL, MESH: Adult, Cholesterol, LDL, MESH: Body Composition, medicine.disease, Kidney Transplantation, MESH: Male, MESH: Prospective Studies, Surgery, MESH: France, Transplantation, Nutrition Assessment, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Body mass index
Abstract

International audience; Recent data suggest that the nutritional status of patients who are on the waiting list for kidney transplantation, influence outcomes after renal transplantation. Body composition (BC) analysis is rarely included in pretransplant evaluation. The aim of this study was to determine how alteration of the BC of these patients could influence pretransplant and post-transplant care. We compared the BC of French patients on a waiting list for kidney transplantation to a sex- and age-matched healthy, European control population. Patients were included when listed for kidney grafting in a prospective longitudinal study (CORPOS). Biological nutritional parameters, fat free mass (FFM) and fat mass (FM) estimated by dual-energy x-ray absorptiometry (DXA) were assessed on the day of wait-list registration. FFM and FM index (FFMi - FMi) are the ratio of FFM and FM to height squared. Results are expressed as median (range). These indexes were compared with previous study values used as a normal range in nutritional assessment and clinical practice. The study included 28 women and 70 men aged 25.3 to 65.9 y. Body mass index ranged from 16.8 kg/m² to 39.4 kg/m². Compared with controls, FMi was higher in women (10.6 kg/m² [3.7-18.6 kg/m²]) than in men (8.1 kg/m² [3.5-13.3 kg/m²] in M) and FFMi was lower in women (14.3 kg/m² [11.8-21.4 kg/m²]) than in men (17.9 kg/m² [13.9-24.2 kg/m²]) (P < 0.01), reflecting an abnormal distribution of body compartments. All biological parameters were within the normal range. BC abnormalities, which can only be detected with the use of DXA, are present in patients on a kidney transplantation waiting list. Detection of these abnormalities could influence the post-transplantation survey in order to prevent the frequent risk for developing metabolic complications after the procedure.

Published
2014

15. Pro-fibrotic activity of lysophosphatidic acid in adipose tissue: In vivo and in vitro evidence

Author

Jean-Loup Bascands, Pauline Decaunes, Philippe Valet, Chloé Rancoule, Jean Sébastien Saulnier-Blache, Sandra Grès, Nathalie Viguerie, Manon Viaud, Anne Bouloumié, Dominique Langin, 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), Service de Biochimie, 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, 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, Mice, Obese, Adipose tissue, Tissue Culture Techniques, Mice, chemistry.chemical_compound, 0302 clinical medicine, Transforming Growth Factor beta, Fibrosis, MESH: Collagen, Lysophosphatidic acid, MESH: Receptors, Lysophosphatidic Acid, MESH: Animals, MESH: Propionates, Receptors, Lysophosphatidic Acid, Receptor, MESH: Mice, Obese, 0303 health sciences, MESH: Indazoles, Adipose Tissue, 030220 oncology & carcinogenesis, MESH: Fibrosis, Female, lipids (amino acids, peptides, and proteins), Collagen, Autotaxin, MESH: Adipose Tissue, medicine.medical_specialty, Indazoles, Enzyme Activators, Biology, MESH: Actins, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, MESH: Lysophospholipids, 03 medical and health sciences, In vivo, Internal medicine, medicine, Animals, Humans, MESH: Enzyme Activators, MESH: Tissue Culture Techniques, MESH: Mice, Molecular Biology, MESH: Transforming Growth Factor beta, 030304 developmental biology, MESH: Humans, Isoxazoles, Cell Biology, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Actins, MESH: Male, In vitro, CTGF, Endocrinology, MESH: Isoxazoles, chemistry, Lysophospholipids, Propionates, MESH: Female
Abstract

International audience; Lysophosphatidic acid (LPA) is a pro-fibrotic mediator acting via specific receptors (LPARs) and is synthesized by autotaxin, that increases with obesity. We tested whether LPA could play a role in adipose tissue (AT)-fibrosis associated with obesity. Fibrosis [type I, III, and IV collagens (COL), fibronectin (FN), TGFβ, CTGF and αSMA] and inflammation (MCP1 and F4/80) markers were quantified: (i) in vivo in inguinal (IAT) and perigonadic (PGAT) AT from obese-diabetic db/db mice treated with the LPAR antagonist Ki16425 (5mg/kg/day ip for 7 weeks); and (ii) in vitro in human AT explants in primary culture for 72h in the presence of oleoyl-LPA (10μM) and/or Ki16425 (10μM) and/or the HIF-1α inhibitor YC-1 (100μM). Treatment of db/db mice with Ki16425 reduced Col I and IV mRNAs in IAT and PGAT while Col III mRNAs were only reduced in IAT. This was associated with reduction of COL protein staining in both IAT and PGAT. AT explants showed a spontaneous and time-dependent increase in ATX expression and production of LPA in the culture medium, along with increased levels of Col I and III, TGFβ and αSMA mRNAs and of COL protein staining. In vitro fibrosis was blocked by Ki16425 and was further amplified by oleoyl-LPA. LPA-dependent in vitro fibrosis was blocked by co-treatment with YC1. Our results show that endogenous and exogenous LPA exert a pro-fibrotic activity in AT in vivo and in vitro. This activity could be mediated by an LPA1R-dependent pathway and could involve HIF-1α.

Published
2014

16. 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

17. Control of bone and fat mass by oxytocin

Author

Ez-Zoubir Amri, Didier F. Pisani, 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), RUIZ, Caroline, Université Nice Sophia Antipolis (1965 - 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Osteoporosis, Type 2 diabetes, Overweight, Oxytocin, Bone and Bones, Bone remodeling, 03 medical and health sciences, chemistry.chemical_compound, Mice, Endocrinology, Adipocyte, Internal medicine, Oxytocics, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, MESH: Oxytocin, Animals, Humans, MESH: Animals, Molecular Biology, MESH: Mice, [SDV.BDD]Life Sciences [q-bio]/Development Biology, MESH: Humans, business.industry, MESH: Oxytocics, General Medicine, MESH: Bone and Bones, medicine.disease, Obesity, Oxytocin receptor, 3. Good health, 030104 developmental biology, chemistry, Adipose Tissue, medicine.symptom, business, MESH: Adipose Tissue, medicine.drug, MESH: Osteoporosis
Abstract

Osteoporosis and overweight/obesity constitute major worldwide public health burdens. Aging is associated with a decrease in hormonal secretion, lean mass and bone mass, and an increase in fat accumulation. It is established that both obesity and osteoporosis are affected by genetic and environmental factors, bone remodeling and adiposity are both regulated through the hypothalamus and sympathetic nervous system. Oxytocin (OT), belongs to the pituitary hormone family and regulates the function of peripheral target organs, its circulating levels decreased with age. Nowadays, it is well established that OT plays an important role in the control of bone and fat mass and their metabolism. Of note, OT and oxytocin receptor knock out mice develop bone defects and late-onset obesity. Thus OT emerges as a promising molecule in the treatment of osteoporosis and obesity as well as associated metabolic disorders such as type 2 diabetes and cardiovascular diseases. In this review, we will discuss findings regarding the OT effects on bone and fat mass.

Published
2016

18. Association between Lean and Fat Mass and Indicators of Bone Health in Prepubertal Caucasian Children

Author

Angelo Tremblay, Mélanie Henderson, Nathalie Alos, Marie Lambert, Khady Kâ, Belinda Nicolau, Jennifer O'Loughlin, Marie-Claude Rousseau, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Oral Health and Society Unit, Faculty of Dentistry, McGill University = Université McGill [Montréal, Canada], Department of Pediatrics, CHU Sainte-Justine, CHU Ste Justine, Institut National de santé publique du Québec (INSPQ), Institut National de Santé Publique du Québec [Canada] (INSPQ), Département de médecine sociale et préventive, and Université de Montréal (UdeM)

Subjects
Male, medicine.medical_specialty, Bone density, Endocrinology, Diabetes and Metabolism, Osteoporosis, MESH: Absorptiometry, Photon, Bone and Bones, Absorptiometry, Photon, MESH: Cross-Sectional Studies, Endocrinology, Bone Density, MESH: Child, Internal medicine, medicine, Humans, Child, MESH: Bone Density, Dual-energy X-ray absorptiometry, Adiposity, MESH: Adiposity, Bone mineral, Bone growth, MESH: Humans, medicine.diagnostic_test, business.industry, Body Weight, MESH: Bone and Bones, medicine.disease, Obesity, MESH: Male, MESH: Body Weight, Cross-Sectional Studies, Adipose Tissue, Pediatrics, Perinatology and Child Health, Cohort, Lean body mass, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, MESH: Adipose Tissue
Abstract

Background/Aims: Childhood and adolescence are critical periods for bone growth. The independent association between lean and fat mass and indicators of bone health in children is not yet known. We aim to examine the association between each of lean and fat mass and indicators of bone health in 8- to 10-year-old prepubertal Caucasian children. Methods: We present a cross-sectional analysis of baseline data from the QUebec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort which study the natural history of obesity. Study participants (n = 483) included prepubertal children aged 8-10 years and their biological parents. Whole-body bone mineral content (BMC, g), bone area (cm2), bone mineral density (BMD, g/cm2), lean mass (kg), and fat mass (kg) were measured by dual-energy X-ray absorptiometry. Data analyses include multiple linear regressions adjusted for potential confounding variables. Results: A 1-kg increase in lean mass was associated with 28.42 g, 19.88 cm2, and 0.007 g/cm2 increase in whole-body BMC, bone area and BMD respectively. A 1-kg increase in fat mass was associated with 9.32 g, 8.02 cm2, and 0.002 g/cm2 increase in whole-body BMC, bone area and BMD, respectively. Conclusion: Increasing lean mass in children may help optimize bone acquisition and prevent future osteoporosis.

Published
2013

19. Apelin, a promising target for type 2 diabetes treatment?

Author

Claude Knauf, Isabelle Castan-Laurell, Philippe Valet, Cédric Dray, Oxana Kunduzova, 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), and Simon, Marie Francoise

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Adipose tissue, 030209 endocrinology & metabolism, Type 2 diabetes, Biology, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Internal medicine, Small peptide, medicine, Humans, MESH: Intercellular Signaling Peptides and Proteins, 030304 developmental biology, 0303 health sciences, MESH: Humans, MESH: Models, Biological, Type 2 Diabetes Mellitus, Metabolism, medicine.disease, Obesity, Apelin, MESH: Insulin Resistance, Adipose Tissue, Diabetes Mellitus, Type 2, Intercellular Signaling Peptides and Proteins, Insulin Resistance, MESH: Adipose Tissue, MESH: Diabetes Mellitus, Type 2
Abstract

International audience; Insulin resistance is a main feature of obesity and type 2 diabetes mellitus (T2DM). Several mechanisms linking obesity to insulin resistance have been proposed. Adipose tissue modulates metabolism by secreting a variety of factors, which exhibit altered production during obesity. Apelin, a small peptide present in a number of tissues and also produced and secreted by adipocytes, has emerged as a new player with potent functions in energy metabolism, and in insulin sensitivity improvement. In this review, we describe the various metabolic functions that are affected by apelin and we present an integrated overview of recent findings that collectively propose apelin as a promising target for the treatment of T2DM.

Published
2012

20. Decreasing dietary linoleic acid promotes long chain omega-3 fatty acid incorporation into rat retina and modifies gene expression

Author

Stéphane Grégoire, Lionel Bretillon, Catherine Creuzot-Garcher, Niyazi Acar, Bertrand Bardet, Emilie Simon, Alain M. Bron, 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), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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 Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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), INRA (Human Nutrition Department, France), Laboratoires Horus Pharma (Saint Laurent du Var, France) 29000305, and Regional Council of Burgundy (France) 29000362

Subjects
CD36 Antigens, Male, MESH : RNA, Messenger, MESH: 5-Lipoxygenase-Activating Proteins, MESH : Receptors, LDL, MESH: Electroretinography, 0302 clinical medicine, MESH: Fatty Acids, Omega-3, MESH: Animals, MESH : Retinal Ganglion Cells, chemistry.chemical_classification, 0303 health sciences, MESH : Gene Expression Regulation, MESH : Electroretinography, MESH: Retina, MESH: Chromatography, Gas, MESH: Dietary Fats, Unsaturated, docosahexaenoic acid, polyunsaturated fatty acid, Sensory Systems, 3. Good health, nutrition, MESH: Photic Stimulation, Adipose Tissue, MESH: Adipose Tissue, medicine.medical_specialty, Chromatography, Gas, macular degeneration, Linoleic acid, MESH : Arachidonate 12-Lipoxygenase, Arachidonate 12-Lipoxygenase, MESH : Adipose Tissue, MESH: Arachidonate 12-Lipoxygenase, pufa, 03 medical and health sciences, MESH : Dietary Fats, Unsaturated, lipid, Electroretinography, Rats, Long-Evans, RNA, Messenger, MESH: Linoleic Acid, MESH: Antigens, CD36, MESH : Retina, Fatty acid, MESH: Retinal Ganglion Cells, eye diseases, Ophthalmology, Endocrinology, chemistry, MESH: Receptors, LDL, 030221 ophthalmology & optometry, ATP-Binding Cassette Transporters, n 3, MESH: Female, Photic Stimulation, MESH: Liver, Retinal Ganglion Cells, retina, MESH : 5-Lipoxygenase-Activating Proteins, genetic structures, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, retinal pigment epithelium, electroretinogram, MESH : Photic Stimulation, Adipose tissue, angiogenesis, chemistry.chemical_compound, MESH : Female, MESH : Rats, Long-Evans, 2. Zero hunger, medicine.diagnostic_test, MESH : Rats, MESH: Real-Time Polymerase Chain Reaction, MESH: Gene Expression Regulation, MESH : Antigens, CD36, medicine.anatomical_structure, Liver, ALOX12, Biochemistry, MESH: ATP-Binding Cassette Transporters, Female, ATP Binding Cassette Transporter 1, Polyunsaturated fatty acid, MESH : Fatty Acids, Omega-3, MESH: Rats, brain, MESH : Male, 5-Lipoxygenase-Activating Proteins, MESH : Real-Time Polymerase Chain Reaction, rhesus monkey, Biology, Real-Time Polymerase Chain Reaction, MESH : Chromatography, Gas, Linoleic Acid, Cellular and Molecular Neuroscience, Dietary Fats, Unsaturated, MESH : Linoleic Acid, MESH: Rats, Long-Evans, Internal medicine, Fatty Acids, Omega-3, medicine, Animals, MESH : ATP-Binding Cassette Transporters, Omega 3 fatty acid, MESH: RNA, Messenger, 030304 developmental biology, deficient diet, Retinal pigment epithelium, MESH : Liver, MESH: Male, Rats, Gene Expression Regulation, Receptors, LDL, gene expression, MESH : Animals, sense organs, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Age-related macular degeneration (AMD) may be partially prevented by dietary habits privileging the consumption of ω3 long chain polyunsaturated fatty acids (ω3s) while lowering linoleic acid (LA) intake. The present study aimed to document whether following these epidemiological guidelines would enrich the neurosensory retina and RPE with ω3s and modulate gene expression in the neurosensory retina. Rat progenitors and pups were fed with diets containing low or high LA, and low or high ω3s. After scotopic single flash and 8-Hz-Flicker electroretinography, rat pups were euthanized at adulthood. The fatty acid profile of the neurosensory retina, RPE, liver, adipose tissue and plasma was analyzed using gas chromatography. Gene expression was analyzed with real-time PCR in the neurosensory retina. Diets rich in ω3s efficiently improved the incorporation of ω3s into the organs and tissues. This raising effect was magnified by lowering LA intake. Compared to a diet with high LA and low ω3s, low LA diets significantly upregulated LDL-receptor gene expression. Similar but not significant upregulation of CD36, ABCA1, ALOX5 and ALOX12 gene expression was observed in rats fed with low LA. No effect was observed on retinal function. Increasing the intake in ω3s and lowering LA improved the enrichment with ω3s of the tissues, including the neurosensory retina and RPE, and upregulated genes involved in lipid trafficking in the neurosensory retina. Those results consistently reinforced the beneficial role of ω3s in the prevention of AMD, especially when the diet contained low levels of LA, as suggested from epidemiological data.

Published
2011

21. Drug-induced toxicity on mitochondria and lipid metabolism: Mechanistic diversity and deleterious consequences for the liver

Author

Julie Massart, Bernard Fromenty, Annie Borgne-Sanchez, Karima Begriche, Marie-Anne Robin, Department of Metabolism and Aging, The Scripps Research Institute, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Mitologics SAS, Hôpital Robert Debré, The Scripps Research Institute [La Jolla, San Diego], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Brébion, Alice

Subjects
Leptin, MESH: Oxidation-Reduction, MESH: Cell Death, Steatosis, MESH: Carbohydrate Metabolism, Microvesicular Steatosis, Mitochondria, Liver, Mitochondrial Membrane Transport Proteins, Oxidative Phosphorylation, 0302 clinical medicine, Nonalcoholic fatty liver disease, MESH: Obesity, MESH: Animals, MESH: Fatty Liver, MESH: Lipid Metabolism, Liver injury, 0303 health sciences, Fatty Acids, MESH: Energy Metabolism, MESH: Genetic Predisposition to Disease, Drugs, MESH: Reactive Oxygen Species, MESH: Mitochondrial Membrane Transport Proteins, MESH: Adiponectin, Hepatitis C, Lipids, Mitochondria, MESH: Fatty Acids, 3. Good health, MESH: Insulin Resistance, Mitochondrial respiratory chain, Adipose Tissue, 030220 oncology & carcinogenesis, Carbohydrate Metabolism, Adiponectin, MESH: Genome, Mitochondrial, Chemical and Drug Induced Liver Injury, MESH: Mitochondria, Liver, Oxidation-Reduction, MESH: Adipose Tissue, MESH: Diabetes Mellitus, Type 2, Cell death, MESH: Drug-Induced Liver Injury, medicine.medical_specialty, Biology, Models, Biological, 03 medical and health sciences, MESH: Oxidative Phosphorylation, Internal medicine, medicine, Animals, Humans, Genetic Predisposition to Disease, Obesity, 030304 developmental biology, MESH: Hepatitis C, MESH: Humans, Hepatology, Mitochondrial Permeability Transition Pore, Hepatotoxicity, MESH: Models, Biological, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Lipid metabolism, MESH: Leptin, Lipid Metabolism, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Fatty Liver, Endocrinology, Diabetes Mellitus, Type 2, MESH: Alcoholic Intoxication, Mitochondrial permeability transition pore, Oxidative stress, Genome, Mitochondrial, Insulin Resistance, Steatohepatitis, Energy Metabolism, Reactive Oxygen Species, Alcoholic Intoxication
Abstract

International audience; Numerous investigations have shown that mitochondrial dysfunction is a major mechanism of drug-induced liver injury, which involves the parent drug or a reactive metabolite generated through cytochromes P450. Depending of their nature and their severity, the mitochondrial alterations are able to induce mild to fulminant hepatic cytolysis and steatosis (lipid accumulation), which can have different clinical and pathological features. Microvesicular steatosis, a potentially severe liver lesion usually associated with liver failure and profound hypoglycemia, is due to a major inhibition of mitochondrial fatty acid oxidation (FAO). Macrovacuolar steatosis, a relatively benign liver lesion in the short term, can be induced not only by a moderate reduction of mitochondrial FAO but also by an increased hepatic de novo lipid synthesis and a decreased secretion of VLDL-associated triglycerides. Moreover, recent investigations suggest that some drugs could favor lipid deposition in the liver through primary alterations of white adipose tissue (WAT) homeostasis. If the treatment is not interrupted, steatosis can evolve toward steatohepatitis, which is characterized not only by lipid accumulation but also by necroinflammation and fibrosis. Although the mechanisms involved in this aggravation are not fully characterized, it appears that overproduction of reactive oxygen species by the damaged mitochondria could play a salient role. Numerous factors could favor drug-induced mitochondrial and metabolic toxicity, such as the structure of the parent molecule, genetic predispositions (in particular those involving mitochondrial enzymes), alcohol intoxication, hepatitis virus C infection, and obesity. In obese and diabetic patients, some drugs may induce acute liver injury more frequently while others may worsen the pre-existent steatosis (or steatohepatitis).

Published
2011

22. 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

23. Liver methylene fraction by dual- and triple-echo gradient-echo imaging at 3.0T: Correlation with proton MR spectroscopy and estimation of robustness after SPIO administration

Author

David Masson, Patrick Hillon, Isabelle Robin, Romaric Loffroy, Boris Guiu, Serge Aho, Jean-Michel Petit, Bruno Vergès, Jean-Pierre Cercueil, Douraied Ben Salem, Denis Krausé, Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité de Génétique Moléculaire Animale (UGMA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), Service d'Ophtalmologie (CHU de Dijon), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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), Service de Diabétologie, Service d'Hépato-Gastroentérologie, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité de Génétique Moléculaire Animale (UMR GMA), Université de Brest (UBO)-Université de Brest (UBO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Unité de Génétique Moléculaire Animale ( UGMA ), Université de Limoges ( UNILIM ) -Institut National de la Recherche Agronomique ( INRA ), Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), 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 Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )

Subjects
Male, Magnetic Resonance Spectroscopy, MESH : Fatty Liver, MESH: Echo-Planar Imaging, [SDV]Life Sciences [q-bio], Carbon Compounds, Inorganic, MESH : Statistics as Topic, Statistics as Topic, MESH : Aged, Contrast Media, MESH : Carbon Compounds, Inorganic, MESH : Tissue Distribution, 030218 nuclear medicine & medical imaging, Correlation, chemistry.chemical_compound, 0302 clinical medicine, MESH : Dextrans, Non-alcoholic Fatty Liver Disease, MESH : Female, Tissue Distribution, MESH: Dextrans, Methylene, Magnetite Nanoparticles, MESH: Fatty Liver, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Echo-Planar Imaging, Dextrans, Nuclear magnetic resonance spectroscopy, MESH : Adult, Middle Aged, MESH: Reproducibility of Results, Adipose Tissue, Liver, Female, 030211 gastroenterology & hepatology, MESH : Sensitivity and Specificity, Protons, MESH: Adipose Tissue, Adult, Iron Overload, MESH : Male, MESH: Magnetite Nanoparticles, MESH : Adipose Tissue, Sensitivity and Specificity, MESH: Iron Overload, 03 medical and health sciences, Flip angle, Robustness (computer science), MESH: Contrast Media, Linear regression, medicine, MESH : Protons, Humans, MESH : Middle Aged, Radiology, Nuclear Medicine and imaging, MESH: Tissue Distribution, MESH: Statistics as Topic, Aged, MESH : Contrast Media, MESH : Iron Overload, MESH: Humans, MESH : Echo-Planar Imaging, [ SDV ] Life Sciences [q-bio], MESH: Magnetic Resonance Spectroscopy, business.industry, MESH : Reproducibility of Results, MESH : Humans, MESH: Biological Markers, MESH: Carbon Compounds, Inorganic, MESH : Liver, MESH : Magnetite Nanoparticles, Reproducibility of Results, MESH: Adult, Magnetic resonance imaging, MESH: Male, MESH: Sensitivity and Specificity, Proton mr spectroscopy, MESH : Biological Markers, Fatty Liver, chemistry, MESH : Magnetic Resonance Spectroscopy, MESH: Protons, Nuclear medicine, business, MESH: Female, Biomarkers, MESH: Liver
Abstract

Purpose To assess the systematic errors in liver methylene fraction (LMF) resulting from fat–fat interference effects with dual- and triple-echo gradient-recalled-echo Dual/Triple GRE) sequences and to test the robustness of these sequences after iron overloading. Materials and Methods Forty type-2 diabetic patients underwent LMF measurement by 3.0T 1H magnetic resonance spectroscopy (corrected for T1 and T2 decays) as the reference standard and liver fat fraction (%Fat) measurement by four Dual/Triple GRE sequences with 20° and 60° flip angle (α), corrected for T1 recovery. The same four sequences were repeated in eight patients after ferumoxide injection. Corrections for systematic errors were determined from the linear regressions (spectroscopy LMF values over Dual/Triple GRE %Fat values). Robustness was tested using Wilcoxon's signed-rank test. Results Fat–fat interference effects produced a ∼10% relative systematic error and T2* decay produced a 1.9%–4.2% absolute systematic error in LMF. When comparing before and after ferumoxide, dual-echo imaging with α = 20° and α = 60°, even when corrected, showed absolute differences of 7.23% [2.81%–10.25%] (P = 0.0117) and 5.65% [1.89%–8.216.8%] (P = 0.0117), respectively; compared to only 1.17% [0.08%–2.83%] (P = 0.0251) and 1.15% [0.37%–2.73%] (P = 0.2626) with triple-echo imaging and α = 20° and α = 60°, respectively. Conclusion Triple-echo imaging with α = 60° corrected for both T1 recovery and fat–fat interference effects is robust after superparamagnetic iron oxide (SPIO) administration and can reliably quantify LMF. J. Magn. Reson. Imaging 2011;33:119–127. © 2010 Wiley-Liss, Inc.

Published
2010

24. Lipid mobilization in subcutaneous adipose tissue during exercise in lean and obese humans. Roles of insulin and natriuretic peptides

Author

Vladimir Stich, François Crampes, Marie Adeline Marques, Michel Berlan, Dominique Larrouy, Jan Polak, Isabelle de Glisezinski, Katrien Koppo, Dominique Langin, Max Lafontan, Magda Bajzova, Jens Bülow, Johan Van de Voorde, Department of Sports Medicine, Charles University [Prague] (CU), Department of Pharmacology, Universiteit Gent = Ghent University [Belgium] (UGENT), 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), Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Physiology, Bispebjerg Hospital, 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], Service de médecine du sport, Simon, Marie Francoise, Universiteit Gent = Ghent University (UGENT), 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), 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
Glycerol, Male, Anaerobic Threshold, Phosphodiesterase Inhibitors, Physiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Adipose tissue, Octreotide, MESH: Phosphodiesterase Inhibitors, Catecholamines, 0302 clinical medicine, MESH: Aminophylline, Adrenergic alpha-2 Receptor Agonists, Insulin, MESH: Obesity, MESH: Lipid Metabolism, MESH: Anaerobic Threshold, 0303 health sciences, MESH: Adrenergic beta-Antagonists, Aminophylline, Adipose Tissue, MESH: Young Adult, MESH: Rest, MESH: Cyclic Nucleotide Phosphodiesterases, Type 3, Adrenergic alpha-Agonists, Anaerobic exercise, MESH: Adipose Tissue, medicine.drug, Adult, medicine.medical_specialty, Microdialysis, Rest, Adrenergic beta-Antagonists, 030209 endocrinology & metabolism, MESH: Insulin, Peptide hormone, Young Adult, 03 medical and health sciences, MESH: Glycerol, Physiology (medical), Internal medicine, MESH: Catecholamines, medicine, Humans, Lipolysis, Obesity, MESH: Natriuretic Peptides, Natriuretic Peptides, Exercise, Pancreatic hormone, 030304 developmental biology, MESH: Humans, MESH: Octreotide, business.industry, MESH: Adult, Lipid Metabolism, Cyclic Nucleotide Phosphodiesterases, Type 3, MESH: Male, Endocrinology, MESH: Exercise, Exercise Test, MESH: Adrenergic alpha-Agonists, MESH: Receptors, Adrenergic, alpha-2, MESH: Exercise Test, business
Abstract

International audience; The aim of this study was to evaluate the relative contributions of various hormones involved in the regulation of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise and to assess the impact of obesity on this regulation. Eight lean and eight obese men performed a 60-min cycle exercise bout at 50% of their peak oxygen uptake on two occasions: during intravenous infusion of octreotide (a somatostatin analog) or physiological saline (control condition). Lipolysis in SCAT was evaluated using in situ microdialysis. One microdialysis probe was perfused with the adrenergic blockers phentolamine and propranolol while another probe was perfused with the phosphodiesterase and adenosine receptor inhibitor aminophylline. Compared with the control condition, infusion of octreotide reduced plasma insulin levels in lean (from approximately 3.5 to 0.5 microU/ml) and in obese (from approximately 9 to 2 microU/ml), blunted the exercise-induced rise in plasma GH and epinephrine levels in both groups, and enhanced the exercise-induced natriuretic peptide (NP) levels in lean but not in obese subjects. In both groups, octreotide infusion resulted in higher exercise-induced increases in dialysate glycerol concentrations in the phentolamine-containing probe while no difference in lipolytic response was found in the aminophylline-containing probe. The results suggest that insulin antilipolytic action plays a role in the regulation of lipolysis during exercise in lean as well as in obese subjects. The octreotide-induced enhancement of exercise lipolysis in lean subjects was associated with an increased exercise-induced plasma NP response. Adenosine may contribute to the inhibition of basal lipolysis in both subject groups.

Published
2010

25. 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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26. Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology

Author

Samuel Bernard, Mikael Rydén, Erik Arner, Jonas Frisén, Peter Arner, Tom Britton, Kirsty L. Spalding, Pål O. Westermark, Karolinska Institutet [Stockholm], Institute for Theoretical Biology (ITB), Humboldt University Of Berlin, Department of Mathematics [Sweden] (KTH), Stockholm University, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department of Cell and Molecular Biology [Uppsala], Uppsala University, Institut Camille Jordan (ICJ), 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)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Humboldt-Universität zu Berlin, Institut Camille Jordan [Villeurbanne] (ICJ), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Adipose tissue, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Body Mass Index, Muscle hypertrophy, chemistry.chemical_compound, 0302 clinical medicine, Adipocyte, Blood plasma, Adipocytes, Insulin, MESH: Obesity, MESH: Cell Size, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Fasting, Middle Aged, Hyperplasia, Adipose Tissue, MESH: Young Adult, Female, Original Article, Obesity Studies, MESH: Adipose Tissue, Adult, medicine.medical_specialty, Adolescent, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], MESH: Fasting, 030209 endocrinology & metabolism, MESH: Insulin, Biology, MESH: Body Mass Index, Young Adult, 03 medical and health sciences, Thinness, Internal medicine, Internal Medicine, medicine, Humans, Obesity, MESH: Adipocytes, Aged, Cell Size, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Thinness, MESH: Hyperplasia, Body Weight, MESH: Adult, medicine.disease, MESH: Male, MESH: Body Weight, Endocrinology, chemistry, MESH: Female, Body mass index
Abstract

OBJECTIVE Adipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We investigated factors of putative importance for adipose tissue morphology. RESEARCH DESIGN AND METHODS Subcutaneous adipocyte size and total fat mass were compared in 764 subjects with BMI 18–60 kg/m2. A morphology value was defined as the difference between the measured adipocyte volume and the expected volume given by a curved-line fit for a given body fat mass and was related to insulin values. In 35 subjects, in vivo adipocyte turnover was measured by exploiting incorporation of atmospheric 14C into DNA. RESULTS Occurrence of hyperplasia (negative morphology value) or hypertrophy (positive morphology value) was independent of sex and body weight but correlated with fasting plasma insulin levels and insulin sensitivity, independent of adipocyte volume (β-coefficient = 0.3, P < 0.0001). Total adipocyte number and morphology were negatively related (r = −0.66); i.e., the total adipocyte number was greatest in pronounced hyperplasia and smallest in pronounced hypertrophy. The absolute number of new adipocytes generated each year was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001). The relative death rate (∼10% per year) or mean age of adipocytes (∼10 years) was not correlated with morphology. CONCLUSIONS Adipose tissue morphology correlates with insulin measures and is linked to the total adipocyte number independently of sex and body fat level. Low generation rates of adipocytes associate with adipose tissue hypertrophy, whereas high generation rates associate with adipose hyperplasia.

Published
2009

27. mTOR complex 2 in adipose tissue negatively controls whole-body growth

Author

Johan Auwerx, Michael N. Hall, Nadine Cybulski, Pazit Polak, Markus A. Rüegg, Biozentrum [Basel, Suisse], University of Basel (Unibas), Institut Clinique de la Souris (ICS), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), and Peney, Maité

Subjects
Male, medicine.medical_treatment, MESH: Insulin-Like Growth Factor I, Adipose tissue, Growth, mTORC1, MESH: Base Sequence, Polymerase Chain Reaction, MESH: Mice, Knockout, mTORC2, Mice, Absorptiometry, Photon, MESH: Cholesterol, 0302 clinical medicine, MESH: Animals, Insulin-Like Growth Factor I, MESH: Fatty Liver, Mice, Knockout, 0303 health sciences, Multidisciplinary, TOR Serine-Threonine Kinases, Biological Sciences, MESH: Adiponectin, Cholesterol, Adipose Tissue, Adiponectin, MESH: Adipose Tissue, MESH: DNA Primers, medicine.medical_specialty, Normal diet, MESH: Carrier Proteins, MESH: Absorptiometry, Photon, Biology, 03 medical and health sciences, Internal medicine, medicine, Animals, MESH: Mice, MESH: Protein Kinases, Protein kinase B, PI3K/AKT/mTOR pathway, DNA Primers, 030304 developmental biology, MESH: Growth, Base Sequence, Growth factor, RPTOR, MESH: Polymerase Chain Reaction, MESH: Male, Fatty Liver, Rapamycin-Insensitive Companion of mTOR Protein, Endocrinology, Carrier Proteins, Protein Kinases, 030217 neurology & neurosurgery
Abstract

Mammalian target of rapamycin (mTOR), a highly conserved protein kinase that controls cell growth and metabolism in response to nutrients and growth factors, is found in 2 structurally and functionally distinct multiprotein complexes termed mTOR complex 1 (mTORC1) and mTORC2. mTORC2, which consists of rictor, mSIN1, mLST8, and mTOR, is activated by insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB. Though the role of mTOR in single cells is relatively well characterized, the role of mTOR signaling in specific tissues and how this may contribute to overall body growth is poorly understood. To examine the role of mTORC2 in an individual tissue, we generated adipose-specific rictor knockout mice ( rictor ad−/− ). Rictor ad−/− mice are increased in body size due to an increase in size of nonadipose organs, including heart, kidney, spleen, and bone. Furthermore, rictor ad−/− mice have a disproportionately enlarged pancreas and are hyperinsulinemic, but glucose tolerant, and display elevated levels of insulin-like growth factor 1 (IGF1) and IGF1 binding protein 3 (IGFBP3). These effects are observed in mice on either a high-fat or a normal diet, but are generally more pronounced in mice on a high-fat diet. Our findings suggest that adipose tissue, in particular mTORC2 in adipose tissue, plays an unexpectedly central role in controlling whole-body growth.

Published
2009

28. Atrial natriuretic peptide induces postprandial lipid oxidation in humans

Author

Friedrich C. Luft, Fred C.G.J. Sweep, Michael Boschmann, Cedric Moro, Frauke Adams, Max Lafontan, Jens Jordan, Petra Budziarek, Marie Adeline Marques, Michel Berlan, Gabriele Franke, Andreas L. Birkenfeld, Simon, Marie Francoise, Experimental and Clinical Research Center, Charité and HELIOS-Klinikum, Department of Internal Medicine, Yale School of Medicine [New Haven, Connecticut] (YSM), 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), Department of Chemical Endocrinology, Radboud University Medical Center [Nijmegen]-University of Netherlands, Institute of Clinical Pharmacology, and Hanover Medical School

Subjects
MESH: Oxidation-Reduction, Male, MESH: Atrial Natriuretic Factor, Microdialysis, Endocrinology, Diabetes and Metabolism, Adipose tissue, Blood Pressure, Aetiology, screening and detection [ONCOL 5], Atrial natriuretic peptide, Reference Values, Medicine, MESH: Microdialysis, Infusions, Intravenous, MESH: Energy Metabolism, MESH: Reference Values, MESH: Blood Flow Velocity, MESH: Blood Pressure, Postprandial Period, Lipids, Postprandial, Adipose Tissue, MESH: Postprandial Period, Oxidation-Reduction, MESH: Adipose Tissue, Atrial Natriuretic Factor, Blood Flow Velocity, Blood drawing, Adult, medicine.medical_specialty, Lipolysis, Lipid oxidation, Translational research [ONCOL 3], Internal medicine, Internal Medicine, Humans, MESH: Lipolysis, MESH: Infusions, Intravenous, MESH: Humans, Endocrinology and reproduction [UMCN 5.2], business.industry, Hormonal regulation [IGMD 6], MESH: Adult, MESH: Lipids, MESH: Male, Metabolism, Blood pressure, Endocrinology, Energy Metabolism, business
Abstract

OBJECTIVE—Atrial natriuretic peptide (ANP) regulates arterial blood pressure. In addition, ANP has recently been shown to promote human adipose tissue lipolysis through cGMP-mediated hormone-sensitive lipase activation. We hypothesized that ANP increases postprandial free fatty acid (FFA) availability and energy expenditure while decreasing arterial blood pressure. RESEARCH DESIGN AND METHODS—We infused human ANP (25 ng · kg−1 · min−1) in 12 men (age 32 ± 0.8 years, BMI 23.3 ± 0.4 kg/m2) before, during, and 2 h after ingestion of a standardized high-fat test meal in a randomized, double-blind, cross-over fashion. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings. Metabolism was monitored through venous blood sampling, intramuscular and subcutaneous abdominal adipose tissue microdialysis, and indirect calorimetry. RESULTS—ANP infusion decreased mean arterial blood pressure by 4 mmHg during the postprandial phase (P < 0.01 vs. placebo). At the same time, ANP induced lipolysis systemically (P < 0.05 vs. placebo) and locally in subcutaneous abdominal adipose tissue (P < 0.0001 vs. placebo), leading to a 50% increase in venous glycerol (P < 0.01) and FFA (P < 0.05) concentrations compared with placebo. The increase in FFA availability with ANP was paralleled by a 15% increase in lipid oxidation rates (P < 0.05 vs. placebo), driving a substantial increase in postprandial energy expenditure (P < 0.05 vs. placebo). CONCLUSIONS—Our data identify the ANP system as a novel pathway regulating postprandial lipid oxidation, energy expenditure, and concomitantly arterial blood pressure. The findings could have therapeutic implications.

Published
2008

29. Chemotaxis and Differentiation of Human Adipose Tissue CD34+/CD31− Progenitor Cells: Role of Stromal Derived Factor-1 Released by Adipose Tissue Capillary Endothelial Cells

Author

Sandra De Barros, Marie Maumus, Alexandra Miranville, Rudi Busse, Anne Bouloumié, Coralie Sengenès, 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), Institute of Cardiovascular Physiology, Goethe-Universität Frankfurt am Main, and Simon, Marie Francoise

Subjects
MESH: Cell Differentiation, MESH: Chemotaxis, Receptors, CXCR4, Stromal cell, MESH: Adult Stem Cells, animal diseases, CD34, Adipose tissue, Antigens, CD34, Biology, environment and public health, MESH: Receptors, CXCR4, parasitic diseases, Humans, MESH: Endothelial Cells, Progenitor cell, Cells, Cultured, MESH: Humans, Chemotaxis, Endothelial Cells, MESH: Antigens, CD31, Cell Differentiation, 3T3-L1, MESH: Antigens, CD34, Cell Biology, Chemokine CXCL12, Cell biology, Platelet Endothelial Cell Adhesion Molecule-1, Endothelial stem cell, Adult Stem Cells, enzymes and coenzymes (carbohydrates), Adipose Tissue, cardiovascular system, Molecular Medicine, MESH: Chemokine CXCL12, Stem cell, MESH: Adipose Tissue, MESH: Cells, Cultured, Developmental Biology
Abstract

The native CD34+/CD31− cell population present in the stroma-vascular fraction of human adipose tissue (hAT) displays progenitor cell properties since they exhibit adipocyte- and endothelial cell-like phenotypes under appropriate stimuli. To analyze the signals within hAT regulating their phenotypes, the influence of hAT-derived capillary endothelial cells (CECs) was studied on the chemotaxis and differentiation of the hAT-CD34+/CD31− cells. Conditioned medium from hAT-CECs led to a strong chemotaxis of the hAT-CD34+/CD31− cells that was inhibited with pretreatments with pertussis toxin, CXCR-4 antagonist, or neutralizing antibodies. Furthermore, hAT-CECs produced and secreted the CXCR-4 ligand, that is, the stromal derived factor-1 (SDF-1). Finally, hAT-CECs induced the differentiation of hAT-CD34+/CD31− cells toward an endothelial cell (EC) phenotype. Indeed, hAT-CECs and -CD34+/CD31− cell coculture stimulated in a two-dimensional system the expression of the EC CD31 marker by the hAT-progenitor cells and, in a three-dimensional approach, the formation of capillary-like structures via a SDF-1/CXCR-4 dependent pathway. Thus, the migration and differentiation of hAT progenitor cells are modulated by hAT-CEC-derived factors. SDF-1, which is secreted by hAT-derived CECs, and its receptor CXCR-4, expressed by hAT-derived progenitor cells, may promote chemotaxis and differentiation of hAT-derived progenitor cells and thus contribute to the formation of the vascular network during the development of hAT.Disclosure of potential conflicts of interest is found at the end of this article.

Published
2007

30. Sex Differences in Lipolysis-Regulating Mechanisms in Overweight Subjects: Effect of Exercise Intensity*

Author

François Crampes, I. Harant, Fabien Pillard, Michel Berlan, Claire Thalamas, Marie-Adeline Marques, Max Lafontan, Isabelle de Glisezinski, Cedric Moro, Simon, Marie Francoise, 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), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CIC - Biotherapie - Toulouse, and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Glycerol, Leptin, Male, Microdialysis, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Adipose tissue, Overweight, Body Mass Index, Catecholamines, Endocrinology, Atrial natriuretic peptide, Insulin, MESH: Microdialysis, Nutrition and Dietetics, VO2 max, Adipose Tissue, Female, medicine.symptom, MESH: Adipose Tissue, MESH: Oxygen, medicine.drug, medicine.medical_specialty, Lipolysis, Subcutaneous Fat, MESH: Insulin, MESH: Body Mass Index, Sex Factors, MESH: Subcutaneous Fat, Phentolamine, MESH: Sex Factors, MESH: Glycerol, Receptors, Adrenergic, alpha-2, Internal medicine, MESH: Catecholamines, medicine, Humans, MESH: Lipolysis, MESH: Overweight, Exercise, MESH: Humans, business.industry, MESH: Leptin, MESH: Male, Oxygen, MESH: Exercise, Exercise intensity, MESH: Receptors, Adrenergic, alpha-2, business, MESH: Female
Abstract

International audience; OBJECTIVE: To explore sex differences in the regulation of lipolysis during exercise, the lipid-mobilizing mechanisms in the subcutaneous adipose tissue (SCAT) of overweight men and women were studied using microdialysis. RESEARCH METHODS AND PROCEDURES: Subjects matched for age, BMI, and physical fitness performed two 30-minute exercise bouts in a randomized fashion: the first test at 30% and 50% of their individual maximal oxygen uptake (Vo(2max)) and the second test at 30% and 70% of their Vo(2max). RESULTS: In both groups, an exercise-dependent increment in extracellular glycerol concentration (EGC) was observed. Whatever the intensity, phentolamine [alpha-adrenergic receptor (AR) antagonist] added to a dialysis probe potentiated exercise-induced lipolysis only in men. In a probe containing phentolamine plus propranolol (beta-AR antagonist), no changes in EGC occurred when compared with the control probe when exercise was performed at 30% and 50% Vo(2max). A significant reduction of EGC (when compared with the control probe) was observed in women at 70% Vo(2max). At each exercise power, the plasma non-esterified fatty acid and glycerol concentrations were higher in women. Exercise-induced increase in plasma catecholamine levels was lower in women compared with men. Plasma insulin decreased and atrial natriuretic peptide increased similarly in both groups. DISCUSSION: Overweight women mobilize more lipids (assessed by glycerol) than men during exercise. alpha(2)-Anti-lipolytic effect was functional in SCAT of men only. The major finding is that during low-to-moderate exercise periods (30% and 50% Vo(2max)), lipid mobilization in SCAT relies less on catecholamine-dependent stimulation of beta-ARs than on an increase in plasma atrial natriuretic peptide concentrations and the decrease in plasma insulin.

Published
2007

31. 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

32. 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

33. Automated Quantification of Right Ventricular Fat at Contrast-enhanced Cardiac Multidetector CT in Arrhythmogenic Right Ventricular Cardiomyopathy

Author

Arnaud Denis, Pierre Jaïs, François Laurent, Nicolas Derval, Jatin Relan, Tassadit Aït Ali, Hubert Cochet, Michel Haïssaguerre, Frederic Sacher, Maxime Sermesant, Olivier Corneloup, Mélèze Hocini, A Jadidi, Michel Montaudon, Yuki Komatsu, IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], University Heart Centre Freiburg - Bad Krozingen, CHU Bordeaux [Bordeaux], St Jude Medical, Analysis and Simulation of Biomedical Images (ASCLEPIOS), Inria Sophia Antipolis - Méditerranée (CRISAM), and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)

Subjects
Male, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, media_common.quotation_subject, Heart Ventricles, Cardiomyopathy, Contrast Media, Multidetector ct, Right ventricular cardiomyopathy, Text mining, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, MESH: Contrast Media, Multidetector computed tomography, Multidetector Computed Tomography, Medicine, Contrast (vision), Humans, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Prospective Studies, MESH: Arrhythmogenic Right Ventricular Dysplasia, MESH: Multidetector Computed Tomography, Arrhythmogenic Right Ventricular Dysplasia, media_common, MESH: Humans, MESH: Middle Aged, business.industry, Middle Aged, medicine.disease, MESH: Male, MESH: Prospective Studies, 3. Good health, Adipose Tissue, cardiovascular system, Cardiology, Female, MESH: Heart Ventricles, business, MESH: Female, MESH: Adipose Tissue
Abstract

To evaluate an automated method for the quantification of fat in the right ventricular (RV) free wall on multidetector computed tomography (CT) images and assess its diagnostic value in arrhythmogenic RV cardiomyopathy (ARVC).This study was approved by the institutional review board, and all patients gave informed consent. Thirty-six patients with ARVC (mean age ± standard deviation, 46 years ± 15; seven women) were compared with 36 age- and sex-matched subjects with no structural heart disease (control group), as well as 36 patients with ischemic cardiomyopathy (ischemic group). Patients underwent contrast material-enhanced electrocardiography-gated cardiac multidetector CT. A 2-mm-thick RV free wall layer was automatically segmented and myocardial fat, expressed as percentage of RV free wall, was quantified as pixels with attenuation less than -10 HU. Patient-specific segmentations were registered to a template to study fat distribution. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic value of fat quantification by using task force criteria as a reference.Fat extent was 16.5% ± 6.1 in ARVC and 4.6% ± 2.7 in non-ARVC (P.0001). No significant difference was observed between control and ischemic groups (P = .23). A fat extent threshold of 8.5% of RV free wall was used to diagnose ARVC with 94% sensitivity (95% confidence interval [CI]: 82%, 98%) and 92% specificity (95% CI: 83%, 96%). This diagnostic performance was higher than the one for RV volume (mean area under the ROC curve, 0.96 ± 0.02 vs 0.88 ± 0.04; P = .009). In patients with ARVC, fat correlated to RV volume (R = 0.63, P.0001), RV function (R = -0.67, P = .001), epsilon waves (R = 0.39, P = .02), inverted T waves in V1-V3 (R = 0.38, P = .02), and presence of PKP2 mutations (R = 0.59, P = .02). Fat distribution differed between patients with ARVC and those without, with posterolateral RV wall being the most ARVC-specific area.Automated quantification of RV myocardial fat on multidetector CT images is feasible and performs better than RV volume in the diagnosis of ARVC. Online supplemental material is available for this article.

Published
2015

34. 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

35. Is restrained eating a risk factor for weight gain in a general population?

Author

Arnaud Basdevant, Blandine de Lauzon-Guillain, Jan Karlsson, M. Aline Charles, Monique Romon, Jean-Michel Borys, Kaniewski, Nadine, Epidémiologie cardiovasculaire et métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Département nutrition, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Health Care Research Unit, Sahlgrenska University Hospital [Gothenburg]-University of Gothenburg (GU), Association Fleurbaix-Laventie Ville Santé, Association Fleurbaix Laventie Ville Santé, Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Association Fleurbaix Laventie Ville Santé (FLVS)

Subjects
Male, Medicine (miscellaneous), Overweight, MESH: Research Support, Non-U.S. Gov't, Weight Gain, MESH: Eating, MESH: Linear Models, Body Mass Index, Cohort Studies, Eating, Waist–hip ratio, MESH: Risk Factors, Risk Factors, Surveys and Questionnaires, MESH: Obesity, Longitudinal Studies, MESH: Longitudinal Studies, MESH: Cohort Studies, education.field_of_study, Nutrition and Dietetics, Emotional eating, Skinfold Thickness, Adipose Tissue, Body Composition, Female, medicine.symptom, MESH: Adipose Tissue, Adult, medicine.medical_specialty, Waist, Adolescent, Population, MESH: Body Mass Index, MESH: Cross-Sectional Studies, MESH: Skin, Internal medicine, medicine, Humans, Obesity, education, MESH: Adolescent, MESH: Humans, Waist-Hip Ratio, business.industry, MESH: Questionnaires, MESH: Adult, MESH: Body Composition, medicine.disease, MESH: Male, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cross-Sectional Studies, Endocrinology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Linear Models, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Body mass index, Weight gain, Demography
Abstract

BACKGROUND: In modern societies characterized by abundant and accessible foods, restrained eating may become an adaptive behavior to limit weight gain. OBJECTIVE: We assessed the relations between eating behavior (EB) and adiposity in a general population over a 2-y period. DESIGN: We recruited 466 adults and 271 adolescents in 1999 on a geographical basis to participate in a longitudinal study. At the initial examination and 2 y later, they answered an EB questionnaire, the Three-Factor Eating Questionnaire-R18, which measured cognitive restraint (CR), uncontrolled eating, and emotional eating. On the same occasions, several measures of adiposity were also obtained: body mass index (BMI; in kg/m2), waist circumference, the sum of 4 skinfold thicknesses, and percentage body fat. Relations between EB and adiposity were tested separately in adults and adolescents by using mixed linear regressions after adjustment for age, sex, and (in adolescents) Tanner pubertal stage. RESULTS: At baseline, CR was positively associated with BMI in normal-weight subjects (mean BMI: 21.4 in the lowest to 23.3 in the highest CR quintile; P < 0.001) but not in overweight adults (P = 0.25). Initial CR did not predict change in adiposity variables (BMI change: P = 0.79 in adults, P = 0.57 in adolescents and young adults). Conversely, a high initial BMI was associated with a larger increase in CR (beta = 20.1, P < 0.0001 in adults; beta = 21.7, P = 0.003 in adolescents and young adults). CONCLUSIONS: Restrained eating is strongly associated with adiposity in normal-weight subjects but not in overweight subjects. However, restrained eating does not promote weight gain.

Published
2006

36. Syndecan-1 regulates adipogenesis: new insights in dedifferentiated liposarcoma tumorigenesis

Author

Laurence Bianchini, Christian Dani, Marion Marty, Jean-François Michiels, Bérengère Dadone, Florence Pedeutour, Laure-Emmanuelle Zaragosi, 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
Cancer Research, Cellular differentiation, Adipose tissue, MESH: Flow Cytometry, medicine.disease_cause, Syndecan 1, Immunoenzyme Techniques, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: RNA, Small Interfering, RNA, Small Interfering, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Cells, Cultured, Adipogenesis, MESH: Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, Cell Differentiation, General Medicine, Liposarcoma, Flow Cytometry, 3. Good health, Cell Transformation, Neoplastic, Adipose Tissue, Stem cell, MESH: Adipose Tissue, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH: Syndecan-1, Blotting, Western, MESH: Stem Cells, Biology, Real-Time Polymerase Chain Reaction, MESH: Liposarcoma, MESH: Cell Proliferation, medicine, MESH: Blotting, Western, Humans, RNA, Messenger, Progenitor cell, MESH: Immunoenzyme Techniques, neoplasms, MESH: RNA, Messenger, Cell Proliferation, MESH: Humans, medicine.disease, body regions, MESH: Cell Transformation, Neoplastic, Cancer research, Syndecan-1, Carcinogenesis, MESH: Adipogenesis
Abstract

International audience; Syndecan-1 (SDC1/CD138) is one of the main cell surface proteoglycans and is involved in crucial biological processes. Only a few studies have analyzed the role of SDC1 in mesenchymal tumor pathogenesis. In particular, its involvement in adipose tissue tumors has never been investigated. Dedifferentiated liposarcoma, one of the most frequent types of malignant adipose tumors, has a high potential of recurrence and metastastic evolution. Classical chemotherapy is inefficient in metastatic dedifferentiated liposarcoma and novel biological markers are needed for improving its treatment. In this study, we have analyzed the expression of SDC1 in well-differentiated/dedifferentiated liposarcomas and showed that SDC1 is highly overexpressed in dedifferentiated liposarcoma compared with normal adipose tissue and lipomas. Silencing of SDC1 in liposarcoma cells impaired cell viability and proliferation. Using the human multipotent adipose-derived stem cell model of human adipogenesis, we showed that SDC1 promotes proliferation of undifferentiated adipocyte progenitors and inhibits their adipogenic differentiation. Altogether, our results support the hypothesis that SDC1 might be involved in liposarcomagenesis. It might play a prominent role in the dedifferentiation process occurring when well-differentiated liposarcoma progress to dedifferentiated liposarcoma. Targeting SDC1 in these tumors might provide a novel therapeutic strategy.

Published
2014

37. Changes in physical activity explain paradoxical relationship between baseline physical activity and adiposity changes in adolescent girls: the FLVS II study.: Changes in physical activity and adiposity changes in girl

Author

Barbara Heude, Jean-Michel Borys, Jean-Michel Oppert, Adrien Kettaneh, Valérie Deschamps, Pierre Ducimetière, Agnès Lommez, Marie-Aline Charles, Epidémiologie cardiovasculaire et métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Déterminants Biologiques et Comportementaux des Obésités, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-EA3502, Association Fleurbaix-Laventie Ville Santé, and Association Fleurbaix Laventie Ville Santé

Subjects
Male, Gerontology, Longitudinal study, MESH: Chi-Square Distribution, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Body Mass Index, MESH: Skinfold Thickness, 0302 clinical medicine, MESH: Child, Medicine, Longitudinal Studies, 030212 general & internal medicine, Child, MESH: Longitudinal Studies, 10. No inequality, 2. Zero hunger, education.field_of_study, Nutrition and Dietetics, Age Factors, Skinfold Thickness, Adipose Tissue, Body Composition, Female, MESH: Adipose Tissue, Waist, Adolescent, Population, Physical exercise, Article, MESH: Body Mass Index, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, 030225 pediatrics, Humans, education, Exercise, MESH: Adolescent, MESH: Age Factors, Chi-Square Distribution, MESH: Humans, business.industry, MESH: Body Composition, medicine.disease, Obesity, MESH: Male, El Niño, MESH: Exercise, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Body mass index, Chi-squared distribution, Demography
Abstract

OBJECTIVE: To investigate in adolescents relationships between habitual physical activity (PA) and changes in several indicators of adiposity. DESIGN: Longitudinal population-based study. The Fleurbaix-Laventie Ville Sante II (FLVS II) study in Northern France. SUBJECTS: A total of 222 boys and 214 girls aged 8-18 y, not obese at inclusion. MEASUREMENTS: PA (Modifiable Activity Questionnaire) and adiposity (body mass index (kg/m2), percent body fat by bioimpedance analysis, sum of four skinfolds, waist circumference) were assessed in 1999 and 2001. Adiposity indicators adjusted for age and pubertal stage were compared between groups of baseline PA and between groups of PA changes, separately by sex. RESULTS: At baseline, PA was not associated with adiposity indicators in both sexes. In girls only, being in the group with the highest age-relative level of moderate PA at baseline predicted the highest adiposity gain from baseline to follow-up, for all indicators. After adjustment for baseline values, all adiposity indicators were higher at follow-up in girls who had decreased their relative level of moderate PA during follow-up. In boys, changes in adiposity during follow-up were not significantly different across groups of PA changes. However, the sum of skinfolds at follow-up, adjusted for baseline value, tended to be higher in those who decreased their vigorous PA level and lower in those who increased it. CONCLUSION: In adolescent girls, a decrease in PA rather than inactivity per se may result in increased adiposity over time.

Published
2005

38. Apelin, a Newly Identified Adipokine Up-Regulated by Insulin and Obesity

Author

Charlotte Guigné, Philippe Valet, Anne Mazzucotelli, Jeremie Boucher, Bernard Masri, Danièle Daviaud, Ivan Tack, Christian Carpéné, Bernard Knibiehler, Jean-Sébastien Saulnier-Blache, Isabelle Castan-Laurell, Yves Audigier, Stephane Gesta, 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), Hormones, facteurs de croissance et physiopathologie vasculaire, Pharmacologie Moleculaire et Physiopathologie Renale, and Simon, Marie Francoise

Subjects
medicine.medical_treatment, Adipose tissue, White adipose tissue, Mice, chemistry.chemical_compound, Endocrinology, Adipocyte, Brown adipose tissue, MESH: Up-Regulation, Adipocytes, MESH: Obesity, Insulin, MESH: Animals, Cell Differentiation, MESH: Gene Expression Regulation, Up-Regulation, Apelin, medicine.anatomical_structure, Adipose Tissue, MESH: Hyperinsulinism, Intercellular Signaling Peptides and Proteins, Female, MESH: Adipose Tissue, MESH: Cell Differentiation, medicine.medical_specialty, MESH: Carrier Proteins, MESH: Insulin, Biology, Adipokines, Downregulation and upregulation, MESH: Mice, Inbred C57BL, Hyperinsulinism, Internal medicine, medicine, Animals, Humans, Obesity, MESH: Intercellular Signaling Peptides and Proteins, MESH: Mice, MESH: Adipocytes, Apelin receptor, MESH: Humans, Mice, Inbred C57BL, Gene Expression Regulation, chemistry, Carrier Proteins, MESH: Female
Abstract

The results presented herein demonstrate that apelin is expressed and secreted by both human and mouse adipocytes. Apelin mRNA levels in isolated adipocytes are close to other cell types present in white adipose tissue or other organs known to express apelin such as kidney, heart, and to a lesser extent brown adipose tissue. Apelin expression is increased during adipocyte differentiation stage. A comparison of four different models of obesity in mice showed a large increase in both apelin expression in fat cells and apelin plasma levels in all the hyperinsulinemia-associated obesities and clearly demonstrated that obesity or high-fat feeding are not the main determinants of the rise of apelin expression. The lack of insulin in streptozotocin-treated mice is associated with a decreased expression of apelin in adipocytes. Furthermore, apelin expression in fat cells is strongly inhibited by fasting and recovered after refeeding, in a similar way to insulin. A direct regulation of apelin expression by insulin is observed in both human and mouse adipocytes and clearly associated with the stimulation of phosphatidylinositol 3-kinase, protein kinase C, and MAPK. These data provide evidence that insulin exerts a direct control on apelin gene expression in adipocytes. In obese patients, both plasma apelin and insulin levels were significantly higher, suggesting that the regulation of apelin by insulin could influence blood concentrations of apelin. The present work identifies apelin as a novel adipocyte endocrine secretion and focuses on its potential link with obesity-associated variations of insulin sensitivity status.

Published
2005

39. Differences in mRNA expression of adipocyte-derived factors in response to fasting, refeeding and leptin

Author

Thierry Raclot, Fabrice Bertile, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), and Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Leptin, MESH: Insulin-Like Growth Factor I, Adipose tissue, MESH: Rats, Sprague-Dawley, MESH: Eating, Energy homeostasis, Rats, Sprague-Dawley, Eating, chemistry.chemical_compound, 0302 clinical medicine, Adipocyte, Urea, Resistin, MESH: Proteins, MESH: Animals, Insulin-Like Growth Factor I, mRNA level, 10. No inequality, MESH: Nitrogen, Epididymis, 0303 health sciences, education.field_of_study, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Fasting, MESH: Adiponectin, Adipose Tissue, Intercellular Signaling Peptides and Proteins, Adiponectin, MESH: Membrane Proteins, Prolonged food deprivation, MESH: Adipose Tissue, hormones, hormone substitutes, and hormone antagonists, MESH: Hormones, Ectopic, medicine.medical_specialty, MESH: Rats, Nitrogen, MESH: Epididymis, MESH: Fasting, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, Internal medicine, medicine, Animals, Adiponutrin, RNA, Messenger, MESH: Intercellular Signaling Peptides and Proteins, education, Molecular Biology, MESH: Urea, MESH: RNA, Messenger, 030304 developmental biology, Membrane Proteins, Proteins, MESH: Leptin, Cell Biology, MESH: Male, MESH: Resistin, Rats, Endocrinology, chemistry, Hormones, Ectopic, Macrophage migration inhibitory factor
Abstract

International audience; The present study examines whether and to what extent the profiles of adipose-derived factors are altered in epididymal and subcutaneous adipose tissues of long-term fasted/refed and of fasted rats treated by recombinant leptin. Fasting was characterized by three successive metabolic phases. Minor differences in the time-course and magnitude of response were detected between the two adipose sites. Leptin, adiponectin, resistin, adiponutrin, and insulin-like growth factor-1 (IGF-1) gene expressions differentially decreased according to the fasting duration. mRNA levels reached a minimum in late fasting for these secreted factors, being decreased by 60-90% for adiponectin, resistin, and IGF-1, 95-98% for leptin and by 100% for adiponutrin. Refeeding partially or totally restored their mRNA expression in epididymal adipose. Expression levels of apolipoprotein E (ApoE), angiotensinogen (AGT), adipsin and macrophage migration inhibitory factor (MIF) were either unchanged or slightly affected. In leptin-treated rats, leptin mRNA concentrations were significantly decreased in phase 2 of fasting (by 85%) from levels in control phosphate-buffered saline (PBS)-treated rats in both tissues. Leptin treatment also decreased resistin mRNA levels (by 78% in P2L and 63% in P3L relative to control groups) in subcutaneous adipose. These data suggest that adiponectin, resistin, adiponutrin, and IGF-1 could be involved in overall energy homeostasis during prolonged fasting, as leptin is. The mechanisms that underlie the expressions of these adipose-secreted factors remain to be determined.

Published
2004

40. Fatty acid composition of fats is an early determinant of childhood obesity: a short review and an opinion

Author

P. Guesnet, G. Ailhaud, Institut de signalisation, biologie du développement et cancer (ISBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), LNSA UR909, INRA, Jouy en Josas, Institut National de la Recherche Agronomique (INRA), 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), and Laboratoire de nutrition et sécurité alimentaire

Subjects
LACTATION, MESH: Infant Formula, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Adipose tissue, Overweight, MESH: Gestational Age, Lactation, MESH: Fatty Acids, Omega-6, Adipocytes, MESH: Obesity, Medicine, MESH: Animals, GESTATION, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Omega-6, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, MESH: Milk, Human, Fatty Acids, Cell Differentiation, MESH: Infant, Infant Formula, MESH: Fatty Acids, 3. Good health, Milk, medicine.anatomical_structure, Adipose Tissue, MESH: Dietary Fats, medicine.symptom, MESH: Adipose Tissue, Human, Polyunsaturated fatty acid, MESH: Cell Differentiation, medicine.medical_specialty, ADIPOSE TISSUE DEVELOPMENT, POLYUNSATURATED FATTY ACIDS, Gestational Age, Breast milk, Childhood obesity, 03 medical and health sciences, Fatty Acids, Omega-6, Internal medicine, Animals, Humans, Obesity, MESH: Adipocytes, 030304 developmental biology, MESH: Humans, Milk, Human, business.industry, Public Health, Environmental and Occupational Health, Infant, medicine.disease, Dietary Fats, Endocrinology, chemistry, Infant formula, business
Abstract

International audience; The importance of dietary fat in human obesity remains a controversial issue as the prevalence of overweight and obesity has increased despite no dramatic change in the amount of ingested fats over the past few decades. However, qualitative changes (i.e. the fatty acid composition of fats) have been largely disregarded. In this review, we summarize experimental evidence which supports polyunsaturated fatty acids of the omega6 series as being potent promoters of both adipogenesis in vitro and adipose tissue development in vivo during the gestation/lactation period. This conclusion is also supported by epidemiological data from infant studies as well as by the assessment of the fatty acid composition of mature breast milk and formula milk. It is proposed that unnoticed changes in fatty acid composition of ingested fats over the last decades have been important determinants in the increasing prevalence of childhood overweight and obesity.

Published
2004

41. Comparison of the expression and activity of the lipogenic pathway in human and rat adipose tissue

Author

Vincent Frering, Claudie Pinteur, V. Large, Michel Beylot, Dominique Letexier, Physiopathologie Metabolique et Renale, Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Coenzymes, Adipose tissue, MESH: Rats, Sprague-Dawley, Biochemistry, Body Mass Index, MESH: CCAAT-Enhancer-Binding Proteins, Rats, Sprague-Dawley, 0302 clinical medicine, Endocrinology, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Obesity, MESH: Animals, 2. Zero hunger, fatty acid synthase, messenger ribonucleic acid, 0303 health sciences, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Reverse Transcriptase Polymerase Chain Reaction, MESH: Coenzymes, MESH: Transcription Factors, Lipids, MESH: Gene Expression Regulation, sterol regulatory element binding protein 1c, DNA-Binding Proteins, Fatty acid synthase, Adipose Tissue, Liver, Lipogenesis, Sterol Regulatory Element Binding Protein 1, MESH: Adipose Tissue, MESH: Fatty Acid Synthases, Adult, medicine.medical_specialty, MESH: Rats, stable isotopes, 030209 endocrinology & metabolism, QD415-436, Biology, MESH: Body Mass Index, MESH: Sterol Regulatory Element Binding Protein 1, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, Obesity, RNA, Messenger, Carbohydrate-responsive element-binding protein, carbohydrate response element binding protein, MESH: RNA, Messenger, 030304 developmental biology, Messenger RNA, MESH: Humans, Acetyl-CoA carboxylase, MESH: Adult, Cell Biology, Acetyl-CoA Carboxylase 1, MESH: Lipids, MESH: Male, Rats, Gene Expression Regulation, CCAAT-Enhancer-Binding Proteins, biology.protein, acetyl-CoA carboxylase 1, MESH: Acetyl-CoA Carboxylase, Fatty Acid Synthases, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins, Acetyl-CoA Carboxylase, Transcription Factors, MESH: Liver
Abstract

International audience; Lipogenesis is considered less active in human than in rat adipose tissue. This could be explained by different nutritional conditions, namely high-carbohydrate (HCHO) diet in rats and high-fat (HF) diet in humans. Adipose tissue was sampled (postabsorptive state) in rats and humans receiving HCHO or HF diets, ad libitum fed humans, and obese subjects. We measured 1) mRNA concentrations of fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1), sterol regulatory element binding protein 1c (SREBP-1c), and carbohydrate response element binding protein (ChREBP), 2) SREBP-1c protein, and 3) FAS activity. FAS, ACC1, ChREBP, and SREBP1-c mRNA concentrations were unaffected by diet in humans or in rats. FAS and ACC1 mRNA levels were lower in humans than in rats (P < 0.05). FAS activity was unaffected by diet and was lower in humans (P < 0.05). SREBP-1c mRNA concentrations were similar in rats and humans, but the precursor and mature forms of SREBP-1c protein were less abundant in humans (P < 0.05). ChREBP mRNA concentrations were lower in humans than in rats. In conclusion, the lipogenic capacity of adipose tissue is lower in humans than in rats. This is not related to differences in diet and is probably explained by lower abundance of SREBP-1c protein. A decreased expression of ChREBP could also play a role.

Published
2003

42. Prognostic impact of fat tissue loss and cachexia assessed by computed tomography scan in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Author

Hervé Tilly, Stéphane Leprêtre, Jerome Kraut, Fabrice Jardin, Marie-Laure Fontoura, Romain Modzelewski, Aspasia Stamatoullas, Jean Michel Picquenot, Oana Brehar, Carole Fronville, Vincent Camus, Ali N. Chamseddine, Luminata Groza, Pascal Lenain, Hélène Lanic, Nathalie Cardinael, Emilie Lemasle, Nathalie Contentin, Florian Clatot, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Psychiatrique Universitaire [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Groupe d'étude des proliférations lymphoïdes (GPL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Breton, Céline, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Combined Modality Therapy, Cachexia, MESH: Immunotherapy, [SDV]Life Sciences [q-bio], Gastroenterology, MESH: Aged, 80 and over, 0302 clinical medicine, International Prognostic Index, Medicine, MESH: Aged, 2. Zero hunger, Aged, 80 and over, 0303 health sciences, Hazard ratio, Hematology, General Medicine, Prognosis, Combined Modality Therapy, 3. Good health, [SDV] Life Sciences [q-bio], Adipose Tissue, 030220 oncology & carcinogenesis, Rituximab, Female, Immunotherapy, Lymphoma, Large B-Cell, Diffuse, MESH: Tomography, X-Ray Computed, MESH: Adipose Tissue, medicine.drug, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, Internal medicine, Humans, 030304 developmental biology, Aged, Retrospective Studies, MESH: Humans, business.industry, MESH: Retrospective Studies, medicine.disease, MESH: Male, Confidence interval, Surgery, MESH: Cachexia, Sarcopenia, MESH: Lymphoma, Large B-Cell, Diffuse, business, Tomography, X-Ray Computed, MESH: Female, Body mass index, Diffuse large B-cell lymphoma
Abstract

Objectives Approximately 30% of DLBCL patients are older than 70 yr. This study evaluated the prognostic impact of a cachexia score (CS) including fat tissue loss (adipopenia) and sarcopenia as assessed by computed tomography (CT scan) in elderly DLBCL patients treated with chemotherapy and rituximab (R). Methods This retrospective analysis included 80 DLBCL patients older than 70 yr treated with R-CHOP or R-miniCHOP. Skeletal muscle (SM) and visceral (V) and subcutaneous (S) adipose (A) tissues were measured by analysing CT images at the third lumbar (L3) level. Results The median age of the patients was 78 yr. Forty-four and 46 patients were considered sarcopenic and adipopenic, respectively. The median progression-free survival (PFS) was 13.6 months in the adipopenic group and 49.4 months in the non-adipopenic group [hazard ratio (HR) = 2.27; 95% confidence interval (CI): 1.3–4; P = 0.0042]. The median overall survival (OS) was 25.7 months in the adipopenic group and 57.1 months in the non-adipopenic group (HR = 1.93; 95% CI: 1.05–3.55; P = 0.0342). A two-point CS including adipopenia and sarcopenia was created and defined two distinct risk groups with differences in outcomes that were highly significant. The CS was predictive of the prognosis in a multivariate analysis including body mass index (BMI) (< or ≥25 kg/m2), age (< or ≥80 yr), international prognostic index (IPI) and albuminaemia (HR = 3.67; 95% CI = 1.93–6.97; P

Published
2014

43. Soluble CD163 is associated with CD163 mRNA expression in adipose tissue and with insulin sensitivity in steady-state condition but not in response to calorie restriction

Author

Vladimir Stich, Lenka Rossmeislová, Michaela Šiklová, Jana Kračmerová, Eva Klimcakova, Zuzana Kovacova, Jan Polak, Lucia Mališová, Michaela Tencerová, Dominique Langin, Simon, Marie Francoise, Department of Sport Medicine, Charles University [Prague] (CU), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-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), 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), Laboratoire de biochimie clinique, and CHU Toulouse [Toulouse]

Subjects
Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, Biochemistry, MESH: Glucose Clamp Technique, Cohort Studies, Endocrinology, MESH: Obesity, MESH: Antigens, Differentiation, Myelomonocytic, MESH: Antigens, CD, MESH: Cohort Studies, MESH: Receptors, Cell Surface, 2. Zero hunger, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Aged, MESH: Middle Aged, CD68, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, MESH: Insulin Resistance, Adipose Tissue, MESH: Young Adult, Cohort, Biomarker (medicine), Female, MESH: Adipose Tissue, Adult, medicine.medical_specialty, Calorie restriction, Antigens, Differentiation, Myelomonocytic, Context (language use), Receptors, Cell Surface, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Young Adult, MESH: Cross-Sectional Studies, Antigens, CD, Internal medicine, medicine, Humans, Obesity, RNA, Messenger, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: RNA, Messenger, Aged, Caloric Restriction, MESH: Caloric Restriction, MESH: Humans, Biochemistry (medical), MESH: Adult, Cross-Sectional Studies, Glucose Clamp Technique, Insulin Resistance, Body mass index, CD163, MESH: Female
Abstract

Context: Soluble CD163 (sCD163) was suggested as a biomarker of insulin sensitivity and CD163 mRNA expression representing macrophage content in adipose tissue (AT). Objective: The aim of this study was to investigate, in cross-sectional and prospective design, the relationship between sCD163 circulating levels and CD163 mRNA expression in adipose tissue and insulin sensitivity assessed by euglycemic-hyperinsulinemic clamp. Design, Setting, Participants, and Interventions: Two cohorts of subjects were examined in the study. Cohort 1 included 42 women with a wide range of body mass index (17–48 kg/m2); cohort 2 included 27 obese women who followed a dietary intervention consisting of 1 month of a very low-calorie diet and 5 months of a weight-stabilization period. Main Outcome Measures: Serum levels of CD163 and mRNA expression of CD163 and CD68 in sc and visceral (visc) AT were determined, and insulin sensitivity [expressed as glucose disposal rate (GDR)] was measured in cohort 1. In cohort 2, serum levels of CD163, mRNA expressions of CD163, CD68, and CD163-shedding factors [TNF-α-converting enzyme (TACE) and tissue inhibitor of metalloproteinase (TIMP3)] in sc AT were examined and GDR was measured before and during dietary intervention. Results: In cohort 1, circulating sCD163 correlated with CD163 mRNA levels in both sc and visc AT. sCD163 and CD163 mRNA expression in both fat depots correlated with GDR. In cohort 2, the diet-induced changes of sCD163 levels did not correlate with those of CD163, CD68, TACE, and TIMP3 mRNA levels. Although the pattern of the diet-induced change of sCD163 paralleled that of GDR, there was no correlation between the changes of these two variables. Conclusion: sCD163 correlates with CD163 mRNA expression in sc and visc AT and with whole-body insulin sensitivity in the steady-state condition. These associations are not observed with respect to the diet-induced changes during a weight-reducing hypocaloric diet.

Published
2014

44. 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

45. 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

46. Lysophosphatidic acid synthesis and release

Author

Marie-Françoise Simon, Céline Pagès, Jean Sébastien Saulnier-Blache, Philippe Valet, Saulnier-Blache, Jean Sébastien, Biologie de l'adipocyte, physiologie du tissu adipeux et obésités, Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Louis Bugnard-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Platelet Aggregation, Arteriosclerosis, Physiology, MESH: Biological Transport, Phosphatidic Acids, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Models, Biological, Biochemistry, Fatty acid-binding protein, MESH: Lysophospholipids, chemistry.chemical_compound, Cell surface receptor, Neoplasms, Lysophosphatidic acid, Extracellular, Humans, MESH: Neoplasms, Secretion, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Platelet Aggregation, Pharmacology, MESH: Humans, MESH: Phosphatidic Acids, Kinase, MESH: Models, Biological, Biological Transport, Cell Biology, Cell biology, Adipose Tissue, MESH: Arteriosclerosis, chemistry, lipids (amino acids, peptides, and proteins), Lysophospholipids, biological phenomena, cell phenomena, and immunity, Autotaxin, Gelsolin, MESH: Adipose Tissue
Abstract

Lysophosphatidic acid (LPA) is a bioactive phospholipid controlling numerous cellular responses through the activation of specific G-protein coupled transmembrane receptors. LPA is present in several biological fluids (serum, plasma, aqueous humor) and can be secreted by several cell types (platelets, fibroblasts, adipocytes, cancer cells). Whereas, multiple pathways of synthesis and degradation of LPA have been described, their relative contribution in extracellular secretion and biodisponibility is still a matter of debate. The first part of the present review is devoted to the description of the different enzymes involved in LPA synthesis (acyltransferases, phospholipases, kinases) and degradation (lysophospholipases, lipid-phosphatases), as well as to the molecules involved in LPA transport (albumin, fatty acid binding proteins, gelsolin, lipoproteins). In a second part, the different physio-pathological situations (aggregation, cancer, injuries) associated with LPA production, as well as the potential role played by LPA in genesis of certain diseases (cancer, obesity, arteriosclerosis) are listed and analyzed.

Published
2001

47. 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

48. 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

49. 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

50. 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

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