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1. The Release of Adipose Stromal Cells from Subcutaneous Adipose Tissue Regulates Ectopic Intramuscular Adipocyte Deposition

Author: Quentin Sastourné-Arrey, Célia Bergeaud, Louis Casteilla, Emmanuelle Arnaud, Jean Philippe Pradère, Cedric Moro, Virginie Bourlier, Noémie Juin, Marta Gil-Ortega, Coralie Sengenès, Corinne Barreau, Julie Vion, Amandine Girousse, Christophe Guissard, STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), University of British Columbia (UBC), Service de Pharmacologie Clinique, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR 31 Louis Bugnard (IFR 31), and 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]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, medicine.medical_specialty, Stromal cell, Subcutaneous Fat, Adipose tissue, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Adipocyte, Lipid droplet, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Progenitor cell, lcsh:QH301-705.5, Progenitor, Skeletal muscle, medicine.disease, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, lcsh:Biology (General), Intramuscular Absorption, chemistry, Stromal Cells, 030217 neurology & neurosurgery
Abstract: Summary: Ectopic lipid deposition (ELD) is defined by excess fat storage in locations not classically associated with adipose tissue (AT) storage. ELD is positively correlated with insulin resistance and increased risk of metabolic disorders. ELD appears as lipid droplets or adipocytes, whose cell origin is unknown. We previously showed that subcutaneous AT (ScAT) releases adipocyte progenitors into the circulation. Here, we demonstrate that triggering or preventing the release of adipocyte precursors from ScAT directly promoted or limited ectopic adipocyte formation in skeletal muscle in mice. Importantly, obesity-associated metabolic disorders could be mimicked by causing adipocyte precursor release without a high-fat diet. Finally, during nutrient overload, adipocyte progenitors exited ScAT, where their retention signals (CXCR4/CXCL12 axis) were greatly decreased, and further infiltrated skeletal muscles. These data provide insights into the formation of ELD associated with calorie overload and highlight adipocyte progenitor trafficking as a potential target in the treatment of metabolic diseases. : Girousse et al. show that, in mice fed a high-fat diet, adipose stromal cells (ASCs) can egress subcutaneous adipose tissue and infiltrate skeletal muscle to form ectopic adipocytes, causing metabolic disturbance. ASC trafficking is regulated by the CXCR4/CXCL12 axis, and pioglitazone intermittent treatment can prevent muscle ectopic lipid deposition. Keywords: ectopic adipocytes, adipose stem or stromal cells, intramuscular adipocyte, thiazolidinedione, type 2 diabetes, CXCR4/CXCL12, AMD3100, lymphatic system, chemotaxis
Published: 2019

2. The CKD plasma lipidome varies with disease severity and outcome

Author: Jonas Laget, Jean-Sébastien Saulnier-Blache, Joost P. Schanstra, Klaus M. Weinberger, Ulrika Lundin, Harald Mischak, Flore Duranton, Nathalie Gayrard, Marie-Françoise Servel, Àngel Argilés, Biocommunication en Cardio-Métabolique (BC2M), Université de Montpellier (UM), Equipe 7 Inserm U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université 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), BIOCRATES Life Sciences AG [Innsbruck, Austria], Mosaiques Diagnostics & Therapeutics (MOSAIQUES DIAGNOSTICS & THERAPEUTICS), Mosaiques Diagnostics & Therapeutics AG, Nephrologie - Dialyse St-guilhem [Sète], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de recherche sur les obésités, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Toulouse [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), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Mosaiques Diagnostics and Therapeutics AG, Néphrologie Dialyse Saint Guilhem (NDSG), Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Mosaiques Diagnostics & Therapeutics AG [Hannover, Germany], Private University for Health Sciences, Medical Informatics and Technology [Tirol] (UMIT), sAnalytiCo Ltd [Belfast, UK], and Saulnier-Blache, Jean Sébastien
Subjects: Male, Sphingomyelin, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Gastroenterology, Renal disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Renal Dialysis, Internal medicine, Lipidomics, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Renal Insufficiency, Chronic, ComputingMilieux_MISCELLANEOUS, Aged, Lysophospholipid, chemistry.chemical_classification, Nutrition and Dietetics, business.industry, Fatty acid, Lipid metabolism, Lipidome, Middle Aged, medicine.disease, Lipid Metabolism, Elaidic acid, 3. Good health, [SDV] Life Sciences [q-bio], Primary Prevention, Phospholipid, chemistry, Phosphatidylcholines, Female, Hemodialysis, Cardiology and Cardiovascular Medicine, business, Kidney disease
Abstract: International audience; Background: Various alterations in lipid metabolism have been observed in patients with chronic kidney disease (CKD).Objectives: To determine the levels of lipid species in plasma from CKD and hemodialysis (HD) patients and test their association with CKD severity and patient outcome.Methods: Seventy-seven patients with CKD stage 2 to HD were grouped into classes of CKD severity at baseline and followed-up for 3.5 years for the occurrence of transition to HD or death (combined outcome). Plasma levels of phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), sphingomyelins (SMs), and fatty acids were analyzed by flow-injection analysis coupled to tandem mass spectrometry or gas chromatography coupled with mass spectrometry. Kruskal Wallis rank tests and Cox regressions were used to analyze the association of lipids with CKD severity and the risk of combined outcome, respectively.Results: The plasma level of PCs, LPCs, and SMs was decreased in HD patients compared with nondialyzed CKD patients (all P < .05), whereas esterified and/or nonesterified fatty acids level did not change. Thirty-four lipids displayed significantly lower abundance in plasma of HD patients, whereas elaidic acid (C18:1ω9t) level was increased (P < .001). The total amount of LPCs and individual LPCs were associated with better outcome (P < .05). In particular, LPC 18:2 and LPC 20:3 were statistically associated with outcome in adjusted models (P < .05).Discussion: In HD patients, a reduction in plasma lipids is observed. Some of the alterations, namely reduced LPCs, were associated with the risk of adverse outcome. These changes could be related to metabolic dysfunctions.
Published: 2019

3. Chronic apelin treatment improves hepatic lipid metabolism in obese and insulin-resistant mice by an indirect mechanism

Author: Sophie Le Gonidec, Philippe Valet, Nancy Geoffre, Jean-Philippe Pradere, Jean Personnaz, Cedric Moro, Isabelle Castan-Laurell, C. Bertrand, Aurélie Batut, Katie Louche, Simon Deleruyelle, Bernard Masri, Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Hormones, facteurs de croissance et physiopathologie vasculaire, Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-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 de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Type 2 diabetes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Internal medicine, Diabetes mellitus, Animals, Medicine, Obesity, Triglycerides, ComputingMilieux_MISCELLANEOUS, Apelin receptor, business.industry, Fatty liver, Lipid metabolism, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Lipid Metabolism, medicine.disease, 3. Good health, Apelin, Fatty Liver, 030104 developmental biology, Liver, 030220 oncology & carcinogenesis, Hepatocytes, Insulin Resistance, Steatosis, Energy Metabolism, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Apelin treatment has been shown to improve insulin sensitivity in insulin resistant mice by acting in skeletal muscles. However, the effects of systemic apelin on the hepatic energy metabolism have not been addressed. We thus aimed to determine the effect of chronic apelin treatment on the hepatic lipid metabolism in insulin resistant mice. The apelin receptor (APJ) expression was also studied in this context since its regulation has only been reported in severe liver pathologies. Mice were fed a high-fat diet (HFD) in order to become obese and insulin resistant compared to chow fed mice (CD). HFD mice then received a daily intraperitoneal injection of apelin (0.1 µmol/kg) or PBS during 28 days. Triglycerides content and the expression of different lipogenesis-related genes were significantly decreased in the liver of HFD apelin-treated compared to PBS-treated mice. Moreover, at this stage of insulin resistance, the beta-oxidation was increased in liver homogenates of HFD PBS-treated mice compared to CD mice and reduced in HFD apelin-treated mice. Finally, APJ expression was not up-regulated in the liver of insulin resistant mice. In isolated hepatocytes from chow and HFD fed mice, apelin did not induce significant effect. Altogether, these results suggest that systemic apelin treatment decreases steatosis in insulin resistant mice without directly targeting hepatocytes.
Published: 2018

4. Hypoxia Inhibits Cavin-1 and Cavin-2 Expression and Down-Regulates Caveolae in Adipocytes

Author: Claire Regazzetti, Yannick Le Marchand-Brustel, Philippe Gual, Karine Dumas, Philippe Valet, Pascal Peraldi, Jean-François Tanti, Faustine Pastor, S. Bonnafous, Soazig Le Lay, Sophie Giorgetti-Peraldi, Sandra Lacas-Gervais, Albert Tran, Mireille Cormont, Isabelle Dugail, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Joint Centre for Applied Electron Microscopy, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), 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), Signalisation moléculaire et obésité, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Digestif, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditérannéen de médecine moléculaire (C3M), 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 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (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), 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), and SOLETI, Raffaella
Subjects: Male, [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Adipose tissue, Mice, 0302 clinical medicine, Endocrinology, Caveolae, Adipocytes, RNA, Small Interfering, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, RNA-Binding Proteins, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV] Life Sciences [q-bio], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, 030220 oncology & carcinogenesis, Female, RNA Interference, medicine.symptom, Signal Transduction, Cavin, medicine.medical_specialty, Down-Regulation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Insulin resistance, 3T3-L1 Cells, Internal medicine, medicine, Animals, Humans, Gene silencing, Obesity, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Insulin, Membrane Proteins, Phosphate-Binding Proteins, Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Mice, Inbred C57BL, Oxygen, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Insulin receptor, biology.protein, Carrier Proteins, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: During obesity, a hypoxic state develops within the adipose tissue, resulting in insulin resistance. To understand the underlying mechanism, we analyzed the involvement of caveolae because they play a crucial role in the activation of insulin receptors. In the present study, we demonstrate that in 3T3-L1 adipocytes, hypoxia induces the disappearance of caveolae and inhibits the expression of Cavin-1 and Cavin-2, two proteins necessary for the formation of caveolae. In mice, hypoxia induced by the ligature of the spermatic artery results in the decrease of cavin-1 and cavin-2 expression in the epididymal adipose tissue. Down-regulation of the expression of cavins in response to hypoxia is dependent on hypoxia-inducible factor-1. Indeed, the inhibition of hypoxia-inducible factor-1 restores the expression of cavins and caveolae formation. Expression of cavins regulates insulin signaling because the silencing of cavin-1 and cavin-2 impairs insulin signaling pathway. In human, cavin-1 and cavin-2 are decreased in the sc adipose tissue of obese diabetic patients compared with lean subjects. Moreover, the expression of cavin-2 correlates negatively with the homeostatic model assessment index of insulin resistance and glycated hemoglobin level. In conclusion, we propose a new mechanism in which hypoxia inhibits cavin-1 and cavin-2 expression, resulting in the disappearance of caveolae. This leads to the inhibition of insulin signaling and the establishment of insulin resistance.
Published: 2015

5. Introduced marine macroflora of Lebanon and its distribution on the Levantine coast

Author: Marc Verlaque, Ghazi Bitar, Carlos Valle, Yassine-Ramzi Sghaier, H. El Shaer, Aitor Forcada, Alfonso A. Ramos-Esplá, Oscar H. Ocaña, Universidad de Alicante. Departamento de Ciencias del Mar y Biología Aplicada, Biología Marina, Lebanese University [Beirut] (LU), Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), 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), Blanfuné, Aurélie, and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN)
Subjects: 0106 biological sciences, Environmental Engineering, Caulerpa taxifolia, Eastern Mediterranean, Introduced species, 010501 environmental sciences, Aquatic Science, Oceanography, 01 natural sciences, Invasive species, lcsh:Aquaculture. Fisheries. Angling, invasive species, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Macroflora, Botany, [SDV.EE.ECO] Life Sciences [q-bio]/Ecology, environment/Ecosystems, Marine macroflora, introduced species, invasive species, Lessepsian species, Lebanon, Eastern Mediterranean, Zoología, Marine macroflora, Lebanon, Ecology, Evolution, Behavior and Systematics, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, lcsh:SH1-691, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, biology, Ecology, 010604 marine biology & hydrobiology, Laurencia, biology.organism_classification, introduced species, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, Lessepsian species, Cladophora, Ulva lactuca, Asparagopsis taxiformis, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: The marine macroflora introduced into Lebanon was studied through an analysis of historical data and field studies carried out since 1991. A total of 29 introduced species have been listed: 3 Chromobionta, 13 Rhodobionta, 12 Chlorobionta and 1 Streptobionta. Among them, Caulerpa taxifolia var. distichophylla, Spatoglossum variabile and Womersleyella setacea are recorded for the first time from Lebanon. Among them, Asparagopsis taxiformis, C. taxifolia var. distichophylla, Cladophora patentiramea, Codium arabicum, Codium parvulum, Galaxaura rugosa, Halophila stipulacea, Hypnea cornuta, Laurencia cf. chondrioides, Lophocladia lallemandii, Stypopodium schimperi, Ulva lactuca and Womersleyella setacea are potentially invasive species, and several of them already occupy extensive stretches of the Lebanese coast. The distribution of species on the Levantine coast, their dynamics and the current status of their populations are discussed. The surveys in 2012, 2013 and 2016 were conducted within the framework of the MedMPAnet Project, implemented by UNEP/MAP-RAC/SPA and funded by RAC/SPA, the European Commission (EC), the Spanish Agency for International Cooperation for Development (AECID), and the French Global Environment Facility (FFEM).
Published: 2017

6. Cardiovascular autonomic neuropathy and other complications in type 1 diabetes

Author: Gérard Tap, Brigitte Guidolin, Jean-Michel Senard, Hélène Hanaire, Sébastien Fontaine, Anne Pavy-Le Traon, Simon, Marie Francoise, 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), Facteurs nerveux et structuration tissulaire, Université de Brest (UBO), Service d'explorations fonctionnelles, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Valsalva Maneuver, medicine.medical_treatment, Blood Pressure, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Body Mass Index, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, Diabetic Neuropathies, Diabetes mellitus, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Valsalva maneuver, Humans, Heart rate variability, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Pure autonomic failure, Glycated Hemoglobin, Analysis of Variance, Type 1 diabetes, Models, Statistical, Hand Strength, Endocrine and Autonomic Systems, business.industry, fungi, food and beverages, Baroreflex, Middle Aged, medicine.disease, 3. Good health, Surgery, Diabetes Mellitus, Type 1, Logistic Models, Peripheral neuropathy, Erectile dysfunction, Autonomic Nervous System Diseases, Respiratory Mechanics, Cardiology, Regression Analysis, Female, Neurology (clinical), business, Diabetic Angiopathies, Retinopathy
Abstract: International audience; OBJECTIVE AND METHODS: This study deals with cardiovascular autonomic neuropathy (CAN) in type 1 diabetic patients and its association with other complications. We searched for CAN in 684 patients (age, 47 +/- 12 years; diabetes duration, 22 +/- 11 years) by cardiovascular responses to deep breathing and standing. Patients considered as positive had laboratory evaluation: "Ewing" tests (deep breathing, Valsalva, stand test, hand grip); heart rate variability (HRV) [low frequency (LF) and high frequency (HF) power] and spontaneous baroreflex slope (SBS). Logistic regression was used to identify the combination of patient characteristics, including other complications, most associated with CAN severity according to Ewing Score (ES 0-5). RESULTS: 66.2% presented no significant abnormality (ES 0-0.5), 21.5 % had mild abnormalities (ES 1-2), and 12.3% had confirmed autonomic failure (ES > 2). Decrease in LF, HF and SBS was highly correlated to CAN severity. In the stepwise regression, age, retinopathy, nephropathy, bladder dysfunction, erectile dysfunction, peripheral neuropathy and hypertension remained correlated with CAN, whereas digestive neuropathy, BMI and HbA1c were excluded. Despite a small number of events, we found a significant association between coronary disorders and CAN severity. CONCLUSIONS: Simple bedside tests can detect CAN. HRV and SBS provide additional elements on CAN severity. Diabetes duration did not discriminate sufficiently patients with CAN. The association with retinopathy is in favor of the role of poor glycemic control in CAN development. This study shows the interest of CAN detection and the need to look for extracardiac autonomic neuropathy and silent myocardial ischemia in patients with confirmed CAN.
Published: 2010

7. 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

8. 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

9. Cdk4 promotes adipogenesis through PPARγ activation

Author: Pierre Dubus, Françoise Vignon, Dominique Langin, Lluis Fajas, Anna Abella, Mariano Barbacid, Sushil G. Rane, Marcos Malumbres, Audrey Sicard, Hiroaki Kiyokawa, Endocrinologie moléculaire et cellulaire des cancers, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Histologie et Pathologie Moléculaire, Université Bordeaux Segalen - Bordeaux 2, Centro Nacional de Investigaciones Oncologicas Carlos III, Laboratory of cell regulation and carcinogenesis, Cell Cycle and Human Diseases Group, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, University of Illinois System-University of Illinois System, Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), This work was supported by grants of INSERM (Avenir), FRM, Alfediam, and ARC. Anna Abella is supported by a grant of Inserm Poste Vert. P. Dubus is supported by the Inserm (CreS 4CR03G)., Centro Nacional de Investigaciones Oncologicas / Spanish National Cancer Research Centre [Madrid, Espagne] (CNIO), 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), and Le Ster, Yves
Subjects: endocrine system diseases, Physiology, MESH: Trans, Regulator, Mice, chemistry.chemical_compound, Genes, Reporter, Adipocyte, Adipocytes, E2F1, MESH: Animals, Cyclin, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Adipogenesis, integumentary system, Kinase, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cell cycle, MESH: Gene Expression Regulation, Cell biology, MESH: Glucose, Protein Transport, biological phenomena, cell phenomena, and immunity, Protein Binding, MESH: Protein Transport, endocrine system, medicine.medical_specialty, MESH: Cyclin-Dependent Kinase 4, MESH: Biological Transport, Biology, Transfection, MESH: Mice, Inbred C57BL, 3T3-L1 Cells, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, MESH: Mice, Molecular Biology, MESH: Adipocytes, MESH: RNA, Messenger, MESH: Humans, MESH: Genes, Reporter, Cyclin-Dependent Kinase 4, Biological Transport, Cell Biology, Embryonic stem cell, MESH: 3T3-L1 Cells, Mice, Inbred C57BL, PPAR gamma, enzymes and coenzymes (carbohydrates), Glucose, Endocrinology, Gene Expression Regulation, MESH: PPAR gamma, chemistry, MESH: Adipogenesis
Abstract: SummaryCell cycle regulators such as E2F1 and retinoblastoma (RB) play crucial roles in the control of adipogenesis, mostly by controlling the transition between preadipocyte proliferation and adipocyte differentiation. The serine-threonine kinase cyclin-dependent kinase 4 (cdk4) works in a complex with D-type cyclins to phosphorylate RB, mediating the entry of cells into the cell cycle in response to external stimuli. Because cdk4 is an upstream regulator of the E2F-RB pathway, we tested whether cdk4 was a target for new factors that regulate adipogenesis. Here we find that cdk4 inhibition impairs adipocyte differentiation and function. Disruption of cdk4 or activating mutations in cdk4 in primary mouse embryonic fibroblasts results in reduced and increased adipogenic potential, respectively, of these cells. We show that the effects of cdk4 are not limited to the control of differentiation; cdk4 also participates in adipocyte function through activation of PPARγ.
Published: 2005

10. Production of Lysophosphatidic Acid in Blister Fluid: Involvement of a Lysophospholipase D Activity

Author: Josette Fauvel, Madie Fanguin, Sandra Grès, Hugues Chap, Jean-Pierre Salles, Jean-Sébastien Saulnier-Blache, Clotilde Cariven, Bertrand Perret, Juliette Mazereeuw-Hautier, Service de Dermatologie, CHU Toulouse [Toulouse], 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), Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Dermatologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), and Saulnier-Blache, Jean Sébastien
Subjects: Keratinocytes, Male, wound healing, MESH: Multienzyme Complexes, Biochemistry, chemistry.chemical_compound, Blister, 0302 clinical medicine, MESH: Aged, 80 and over, Cell Movement, Lysophosphatidic acid, Pyrophosphatases, Receptors, Lysophosphatidic Acid, Keratinocyte migration, Receptor, skin and connective tissue diseases, MESH: Cell Movement, Cells, Cultured, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, biology, integumentary system, MESH: Comparative Study, Middle Aged, lysophospholipase D, MESH: Keratinocytes, 3. Good health, Cell biology, Phosphodiesterase I, 030220 oncology & carcinogenesis, Female, lipids (amino acids, peptides, and proteins), biological phenomena, cell phenomena, and immunity, Autotaxin, MESH: Cells, Cultured, Adult, blister fluid, medicine.medical_specialty, skin, MESH: Glycoproteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Dermatology, Article, MESH: Lysophospholipids, MESH: Blister, 03 medical and health sciences, Phospholipase A2, Multienzyme Complexes, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Platelet activation, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Aged, Glycoproteins, 030304 developmental biology, MESH: Humans, Phosphoric Diester Hydrolases, Glucose-6-Phosphate Isomerase, MESH: Adult, Cell Biology, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Male, Endocrinology, chemistry, biology.protein, Alkylglycerophosphoethanolamine phosphodiesterase, Lysophospholipids, Wound healing, MESH: Phosphoric Diester Hydrolases, MESH: Female, lysophosphatidic acid, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Autocrine Motility Factor
Abstract: Lysophosphatidic acid (LPA) is present in abundance in serum resulting from platelet activation and is also found in other biological fluids. LPA controls numerous cellular responses and plays a role in specific functions such as wound healing, especially in the skin. Nevertheless, its presence in the skin has never been investigated. Since re-epithelialization occurs after blister rupture, we tested the presence of endogenous LPA in blister fluid and investigated a possible mechanism for its biosynthesis and biological functions. Using a radioenzymatic assay, LPA was detected in 33 blister fluids originating from 24 bullous dermatoses, and at higher concentrations than in plasma. In parallel, blister fluids contained a lysophospholipase D (LPLD) activity but no detectable phospholipase A2 activity. The expressions of the LPLD autotaxin (ATX) and of LPA1-receptor (LPA1-R) were greatly increased in blister skin when compared with normal skin. Finally, LPA was found to have a positive effect on the migration of cultured keratinocytes. These results show that LPA is present in blister fluid synthesized by the LPLD ATX. Due to its ability to enhance keratinocyte migration, LPA in blister fluid could, via the LPA1-R, play an important role in re-epithelialization occurring after blister rupture.
Published: 2005
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11. 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

12. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer

Author: Ahmed Boucharaba, Claire-Marie Serre, Sandra Grès, Jean Sébastien Saulnier-Blache, Jean-Claude Bordet, Julien Guglielmi, Philippe Clézardin, Olivier Peyruchaud, Saulnier-Blache, Jean Sébastien, Physiopathologie des Osteopathies Fragilisantes, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Unité de recherche sur l'hémophilie et les maladies hémorragiques constitutionnelles - EA3735, and Université de Lyon-Université de Lyon
Subjects: MESH: Cytokines, MESH: Enzyme, MESH: Cell Line, Tumor, MESH: Bone Resorption, MESH: Cricetinae, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, General Medicine, MESH: Bone and Bones, MESH: Bone Neoplasms, MESH: Dose-Response Relationship, Drug, MESH: Cell Line, MESH: Cell Proliferation, MESH: Culture Media, lipids (amino acids, peptides, and proteins), MESH: Animals, MESH: Disease Progression, MESH: Doxycycline, biological phenomena, cell phenomena, and immunity, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Blood Platelets, MESH: Breast Neoplasms
Abstract: The role of lysophosphatidic acid (LPA) in cancer is poorly understood. Here we provide evidence for a role of LPA in the progression of breast cancer bone metastases. LPA receptors LPA(1), LPA(2), and LPA(3) were expressed in human primary breast tumors and a series of human breast cancer cell lines. The inducible overexpression of LPA(1) in MDA-BO2 breast cancer cells specifically sensitized these cells to the mitogenic action of LPA in vitro. In vivo, LPA(1) overexpression in MDA-BO2 cells enhanced the growth of subcutaneous tumor xenografts and promoted bone metastasis formation in mice by increasing both skeletal tumor growth and bone destruction. This suggested that endogenous LPA was produced in the tumor microenvironment. However, MDA-BO2 cells or transfectants did not produce LPA. Instead, they induced the release of LPA from activated platelets which, in turn, promoted tumor cell proliferation and the LPA(1)-dependent secretion of IL-6 and IL-8, 2 potent bone resorption stimulators. Moreover, platelet-derived LPA deprivation in mice, achieved by treatment with the platelet antagonist Integrilin, inhibited the progression of bone metastases caused by parental and LPA(1)-overexpressing MDA-BO2 cells and reduced the progression of osteolytic lesions in mice bearing CHO-beta3wt ovarian cancer cells. Overall, our data suggest that, at the bone metastatic site, tumor cells stimulate the production of LPA from activated platelets, which enhances both tumor growth and cytokine-mediated bone destruction.
Published: 2004

13. Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression

Author: Vassallo, Paula, SIMONCINI, STEPHANIE, Ligi, Isabelle, Château, Anne-Line, Bachelier, Richard, Robert, Stéphane, Morere, Julia, Fernandez, Samantha, Guillet, Benjamin, Marcelli, Maxime, Tellier, Edwige, Pascal, Alain, Simeoni, Umberto, Anfosso, Francine, Magdinier, Frédérique, Dignat-George, Francoise, Sabatier, Florence, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Neonatology, La Conception Hospital, Assistance Publique-Hôpitaux de Marseille and Faculté de Médecine, Université de la Méditerranée - Aix-Marseille 2, Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Division of Neonatology, La Conception Hospital, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), 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), Magdinier, Frederique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Key Points • We demonstrate that PT promotes ECFCs dysfunction by inducing stress-induced premature senescence. • Our data reveal that SIRT1 deficiency drives PT-ECFC senescence, and acts as a critical determinant of the PT-ECFC angiogenic defect. Epidemiological and experimental studies indicate that early vascular dysfunction occurs in low-birth-weight subjects, especially preterm (PT) infants. We recently reported impaired angiogenic activity of endothelial colony-forming cells (ECFCs) in this condition. We hypothesized that ECFC dysfunction in PT might result from premature senescence and investigated the underlying mechanisms. Compared with ECFCs from term neonates (n 5 18), ECFCs isolated from PT (n 5 29) display an accelerated senescence sustained by growth arrest and increased senescence-associated b-galactosidase activity. Increased p16 INK4a expression, in the absence of telomere shortening, indicates that premature PT-ECFC aging results from stress-induced senescence. SIRT1 level, a nicotinamide adenine dinucleotide-dependent deacetylase with anti-aging activities, is dramatically decreased in PT-ECFCs and correlated with gestational age. SIRT1 deficiency is subsequent to epigenetic silencing of its promoter. Transient SIRT1 overexpression or chemical induction by resveratrol treatment reverses senescence phenotype, and rescues in vitro PT-ECFC angiogenic defect in a SIRT1-dependent manner. SIRT1 overexpression also restores PT-ECFC capacity for neovessel formation in vivo. We thus demonstrate that decreased expression of SIRT1 drives accelerated senescence of PT-ECFCs, and acts as a critical determinant of the PT-ECFC angiogenic defect. These findings lay new grounds for understanding the increased cardiovascular risk in individuals born prematurely and open perspectives for therapeutic strategy.
Published: 2014

14. Physical activity and sarcopenia

Author: Jacques Mercier, Fabien Pillard, Dalila Laoudj-Chenivesse, Daniel Rivière, Yves Rolland, Gilles Carnac, Jacques Rami, Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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-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-CHU Toulouse [Toulouse], and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]
Subjects: medicine.medical_specialty, Aging, Sarcopenia, Physical activity, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Muscle, Skeletal, Exercise, ComputingMilieux_MISCELLANEOUS, Aged, Evidence-Based Medicine, Muscle Weakness, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Resistance training, Resistance Training, 030229 sport sciences, Evidence-based medicine, medicine.disease, 3. Good health, Exercise Therapy, Oxidative Stress, Chronic disease, Countermeasure, Geriatrics and Gerontology, Exercise prescription, business, 030217 neurology & neurosurgery
Abstract: Physical activity can be a valuable countermeasure to sarcopenia in its treatment and prevention. In considering physical training strategies for sarcopenic subjects, it is critical to consider personal and environmental obstacles to access opportunities for physical activity for any patient with chronic disease. This article presents an overview of current knowledge of the effects of physical training on muscle function and the physical activity recommended for sarcopenic patients. So that this countermeasure strategy can be applied in practice, the authors propose a standardized protocol for prescribing physical activity in chronic diseases such as sarcopenia.
Published: 2011

15. Exercise-induced lipid mobilization in subcutaneous adipose tissue is mainly related to natriuretic peptides in overweight men

Author: Max Lafontan, Fabien Pillard, I. Harant, Michel Berlan, Claire Thalamas, Isabelle de Glisezinski, François Crampes, Cedric Moro, Marie-Adeline Marques, Eva Klimcakova, 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), 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), Service d'exploration de la fonction respiratoire et de médecine du sport, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de médecine moléculaire de Rangueil (I2MR), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Laboratoire des Adaptations de l'Organisme à l'Exercice Musculaire, Institut de minéralogie et de physique des milieux condensés (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie de l'adipocyte, physiologie du tissu adipeux et obésités, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut Louis Bugnard-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Pharmacocinétique et de Toxicologie [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 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), Service de Pharmacologie Clinique, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche sur les obésités, CHU Toulouse [Toulouse]-Laboratoire, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Université Pierre et Marie Curie - Paris 6 (UPMC)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Franco-Czech Laboratory for Clinical Research on Obesity, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Louis Bugnard-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacocinétique et de Toxicologie clinique [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
Subjects: Blood Glucose, Glycerol, Male, Sympathetic nervous system, Physiology, MESH: Atrial Natriuretic Factor, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Adipose tissue, 030204 cardiovascular system & hematology, Overweight, MESH: Dose-Response Relationship, Drug, Propanolamines, 0302 clinical medicine, Atrial natriuretic peptide, Insulin, Medicine, MESH: Double-Blind Method, MESH: Lipid Mobilization, 0303 health sciences, Cross-Over Studies, Lipid Mobilization, MESH: Adrenergic beta-Antagonists, MESH: Thiophenes, medicine.anatomical_structure, medicine.symptom, Atrial Natriuretic Factor, Adult, medicine.medical_specialty, Microdialysis, Adrenergic beta-Antagonists, Subcutaneous Fat, Physical exercise, Thiophenes, MESH: Insulin, MESH: Cross-Over Studies, 03 medical and health sciences, MESH: Subcutaneous Fat, Double-Blind Method, MESH: Glycerol, Physiology (medical), Internal medicine, Humans, Phentolamine, MESH: Overweight, Exercise, MESH: Propanolamines, Adrenergic alpha-Antagonists, Pancreatic hormone, 030304 developmental biology, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Phentolamine, MESH: Adult, MESH: Male, Endocrinology, MESH: Exercise, MESH: Blood Glucose, MESH: Adrenergic alpha-Antagonists, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Involvement of sympathetic nervous system and natriuretic peptides in the control of exercise-induced lipid mobilization was compared in overweight and lean men. Lipid mobilization was determined using local microdialysis during exercise. Subjects performed 35-min exercise bouts at 60% of their maximal oxygen consumption under placebo or after oral tertatolol [a β-adrenergic receptor (AR) antagonist]. Under placebo, exercise increased dialysate glycerol concentration (DGC) in both groups. Phentolamine (α-AR antagonist) potentiated exercise-induced lipolysis in overweight but not in lean subjects; the α2-antilipolytic effect was only functional in overweight men. After tertatolol administration, the DGC increased similarly during exercise no matter which was used probe in both groups. Compared with the control probe under placebo, lipolysis was reduced in lean but not in overweight men treated with the β-AR blocker. Tertatolol reduced plasma nonesterified fatty acids and insulin concentration in both groups at rest. Under placebo or tertatolol, the exercise-induced changes in plasma nonesterified fatty acids, glycerol, and insulin concentrations were similar in both groups. Exercise promoted a higher increase in catecholamine and ANP plasma levels after tertatolol administration. In conclusion, the major finding of our study is that in overweight men, in addition to an increased α2-antilipolytic effect, the lipid mobilization in subcutaneous adipose tissue that persists during exercise under β-blockade is not dependent on catecholamine action. On the basis of correlation findings, it seems to be related to a concomitant exercise-induced rise in plasma ANP when exercise is performed under tertatolol intake and a decrease in plasma insulin.
Published: 2008

16. Sympathoexcitation increases the QT/RR slope in healthy men: differential effects of hypoxia, dobutamine, and phenylephrine

Author: F.E.S.C. Philippe Van De Borne M.D., Atul Pathak, Marko Gujic, Olivier Xhaet, Boutaïna Najem, Jean-Paul Degaute, Anne Houssiere, Jean-Francois Argacha, Department of Cardiology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), 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), Simon, Marie Francoise, 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), Clinical sciences, Cardio-vascular diseases, and Cardiology
Subjects: Adult, Male, medicine.medical_specialty, Cardiac output, MESH: Phenylephrine, MESH: Anoxia, Phenylephrine/pharmacology, Stimulation, 030204 cardiovascular system & hematology, Heart Conduction System/drug effects, MESH: Heart Conduction System, Phenylephrine, 03 medical and health sciences, 0302 clinical medicine, MESH: Dobutamine, Heart Conduction System, Dobutamine, Physiology (medical), Internal medicine, medicine, Humans, Hypoxia, Hypoxia/physiopathology, MESH: Humans, business.industry, Sympatholytics/pharmacology, Healthy subjects, MESH: Sympatholytics, MESH: Adult, Hypoxia (medical), Differential effects, MESH: Male, Dobutamine/pharmacology, Anesthesia, Sympatholytics, Reflex, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; INTRODUCTION: Dynamic ventricular repolarization assessed by QT/RR slopes studies the effects of modifications in cardiac repolarization independently of variations in RR interval (RR). The effects of changes in sympathetic and vagal activity on the QT/RR slope are controversial. We tested the hypothesis that sympathoexcitation is an important determinant of the QT/RR slope. METHODS AND RESULTS: We compared the effects of a reflex sympathetic activation in response to hypoxia, to the direct effects of the infusion of the beta-adrenergic agent dobutamine, on the QTa (apex) and QTe (end)/RR slopes. Dobutamine was titrated to obtain similar increases in cardiac output than with hypoxia. Cardiac vagal activity was estimated by rMSSD and pNN50. In a second group of healthy subjects, we assessed the effect of a reflex cardiac vagal activation in response to phenylephrine infusion on the same variables. We observed a similar increase in QTa and QTe slopes during hypoxia and dobutamine (both P < 0.017 vs. normoxia), despite divergent changes in cardiac vagal activity, as rMSSD and pNN50 decreased with hypoxia compared to normoxia (P < 0.001) but increased during dobutamine infusion compared to hypoxia (P < 0.017). In contrast, these slopes did not change during the rises in rMSSD and pNN50 elicited by phenylephrine (P > 0.7). CONCLUSION: Beta-adrenergic stimulation induces comparable increases in the QT/RR slopes than hypoxia, but in the presence of a larger cardiac vagal activity. Vagal cardiac activation by phenylephrine does not change the QT slopes. This reveals that the sympathetic system is an important determinant of QT/RR dynamicity in healthy men.
Published: 2008

17. Lipid oxidation according to intensity and exercise duration in overweight men and women

Author: Cedric Moro, Daniel Rivière, I. Harant, Fabien Pillard, Isabelle de Glisezinski, E. Garrigue, Max Lafontan, Michel Berlan, François Crampes, Simon, Marie Francoise, 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Adult, Glycerol, Male, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Overweight, MESH: Body Mass Index, Body Mass Index, Endocrinology, Oxygen Consumption, Sex Factors, MESH: Anthropometry, MESH: Sex Factors, MESH: Glycerol, Lipid oxidation, Internal medicine, Weight management, Lipolysis, Medicine, Humans, MESH: Oxygen Consumption, MESH: Overweight, Respiratory exchange ratio, Exercise, MESH: Lipid Metabolism, MESH: Humans, Nutrition and Dietetics, Anthropometry, business.industry, MESH: Time Factors, VO2 max, MESH: Adult, Lipid Metabolism, MESH: Lipids, Lipids, MESH: Male, Oxygen, MESH: Exercise, Lean body mass, Female, medicine.symptom, business, MESH: Female, Body mass index, MESH: Oxygen
Abstract: International audience; OBJECTIVE: Our objective was to compare the effect of different exercise intensities on lipid oxidation in overweight men and women. RESEARCH METHODS AND PROCEDURES: Nine young, healthy, overweight men and women were studied (age, 31.4 +/- 2.3 and 26.7 +/- 2.1 years; BMI, 27.9 +/- 0.4 and 27.2 +/- 0.5; for men and women, respectively). On one study day, the subjects first performed 30 minutes of cycling exercise at 30% of their maximal oxygen uptake (Vo(2max); E1 session), followed by 30 minutes of exercise at 50% Vo(2max) (E2 session). On a second study day, a similar E1 session was followed by 30 minutes of exercise at 70% Vo(2max) (E3 session). From the gas exchange measurements, the respiratory exchange ratio (RER) and the fat oxidation rate (FOR) were calculated. Plasma concentrations of glycerol and non-esterified fatty acids (NEFAs) were assayed. RESULTS: RER was significantly lower for women during only the E1 session. For both sexes, RER decreased over time during the E2 and E3 sessions. During the E1 session, the FOR per kilogram of lean mass (LM) was higher among women, and it did not change over time despite an increase in plasma NEFAs. FOR per kilogram of LM was higher during the E2 exercise for both sexes. During E2 and E3 sessions, as the exercise time was prolonged, the FOR/kg LM increased simultaneously with the increase in the plasma glycerol. DISCUSSION: Lipid oxidation during exercise is optimized for moderate and lengthy exercise. The enhancement of lipid oxidation occurring over time during moderate- and high-intensity exercises could be, in part, linked to the improvement of lipid mobilization. This fact is discussed to shed light on exercise modalities as a tool for the management of overweight.
Published: 2007

18. The role of endothelial cells in inflamed adipose tissue

Author: K. Lolmède, Anne Bouloumié, Coralie Sengenès, Cyrile Anne Curat, Alexandra Miranville, Simon, Marie Francoise, 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), Institute of Cardiovascular Physiology, and Goethe-Universität Frankfurt am Main
Subjects: Panniculitis, Angiogenesis, Adipose tissue macrophages, MESH: Diabetic Angiopathies, Adipose tissue, Adipokine, Inflammation, Cell Communication, MESH: Atherosclerosis, MESH: Cell Communication, Internal Medicine, medicine, Adipocytes, Macrophage, MESH: Obesity, Humans, MESH: Endothelial Cells, Obesity, MESH: Adipocytes, MESH: Humans, business.industry, MESH: Panniculitis, Macrophages, MESH: Macrophages, Endothelial Cells, MESH: Chemokines, Atherosclerosis, Endothelial stem cell, MESH: Insulin Resistance, medicine.anatomical_structure, Adipose Tissue, Diabetes Mellitus, Type 2, Immunology, Cancer research, MESH: Cell Adhesion Molecules, Bone marrow, medicine.symptom, Chemokines, Insulin Resistance, business, Cell Adhesion Molecules, MESH: Adipose Tissue, Diabetic Angiopathies, MESH: Diabetes Mellitus, Type 2
Abstract: International audience; In recent years, the general concept has emerged that chronic low-grade inflammation can be the condition linking excessive development of adipose tissue (AT) and obesity-associated pathologies such as type II diabetes and atherosclerosis. Moreover, the evidence that the growth of the fat mass was associated with an accumulation of adipose tissue macrophages (ATM) has raised the hypothesis that the development of an inflammatory process within the growing fat mass is a primary event involved in the genesis of systemic metabolic and vascular alterations. As ATM originate from the bone marrow/blood compartment, enhanced macrophage recruitment to growing AT is suspected. However, the mechanisms responsible for attracting the blood cells and their entry into the fat mass remain to be clearly defined. The present review highlights the key role of endothelial cells in the control of the inflammatory process and describes the potential involvement of AT-endothelial cells as well as the factors involved in the regulation of their phenotype in the 'inflamed fat tissue'.
Published: 2007

19. The role of neutral lipases in human adipose tissue lipolysis

Author: Peter Arner, Dominique Langin, Karolinska Institute at the Department of Medicine, Karolinska University Hospital [Stockholm], 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), and Simon, Marie Francoise
Subjects: MESH: Signal Transduction, Human fat, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Lipolysis, Adipose tissue, Hormone-sensitive lipase, White adipose tissue, Models, Biological, MESH: Lipase, Internal medicine, MESH: Polymorphism, Genetic, Genetics, medicine, Adipocytes, MESH: Obesity, Animals, Humans, MESH: Animals, MESH: Lipolysis, Obesity, Lipase, Molecular Biology, MESH: Adipocytes, Lipoprotein lipase, MESH: Sterol Esterase, MESH: Humans, Nutrition and Dietetics, Polymorphism, Genetic, biology, Chemistry, MESH: Models, Biological, Cell Biology, Sterol Esterase, Endocrinology, Biochemistry, Adipose Tissue, Adipose triglyceride lipase, biology.protein, Cardiology and Cardiovascular Medicine, MESH: Adipose Tissue, Signal Transduction
Abstract: International audience; PURPOSE OF REVIEW: The aim of this article is to describe the relative roles of hormone sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis. RECENT FINDINGS: Until recently, only hormone sensitive lipase was considered important for the regulation of lipolysis within fat cells. Recent rodent studies have suggested that adipose triglyceride lipase may, however, be more important. The few human adipose triglyceride lipase studies that have been published point to species differences between humans and rodents. Selective inhibition of hormone sensitive lipase in human fat cells completely counteracts hormone-activated lipolysis, though there is a considerable (>>50%) residual nonhormonal (basal) lipolysis. In rodents, adipose triglyceride lipase enzyme activity is stimulated by a cofactor termed CGI-58. In the absence of CGI-58, lipase activity in fat cells is much higher for hormone sensitive lipase than adipose triglyceride lipase. Hormone sensitive lipase expression is regulated by obesity and body weight reduction (decreased and increased, respectively), but this is not the case for adipose triglyceride lipase. A role of adipose triglyceride lipase in human lipolysis is suggested by studies of gene polymorphisms. SUMMARY: Two lipases the 'old' hormone sensitive lipase and the 'new' adipose triglyceride lipase are of importance for the regulation of lipolysis in rodent fat cells. In humans, adipose triglyceride lipase seems essential for maintaining basal lipolytic activity, while hormone sensitive lipase is the enzyme most responsive to stimulated lipolysis.
Published: 2007

20. Comparative studies of the role of hormone-sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis

Author: Dominique Langin, Mikael Rydén, Lennart Blomqvist, Peter Arner, Ellen E. Blaak, Johan Hoffstedt, Johan W. E. Jocken, Vanessa van Harmelen, Andrea Dicker, Mikael Wirén, Aline Mairal, Humane Biologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: NUTRIM - R1 - Metabolic Syndrome, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department of Surgery, 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, Nutrition and Toxicology, 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), and Simon, Marie Francoise
Subjects: Glycerol, Human fat, Physiology, Endocrinology, Diabetes and Metabolism, Hormone-sensitive lipase, MESH: Down-Regulation, MESH: Lipase, Cohort Studies, chemistry.chemical_compound, Norepinephrine, Adipocyte, Adipocytes, MESH: Obesity, MESH: Cohort Studies, MESH: Sterol Esterase, food and beverages, Biochemistry, MESH: Phospholipases A, Female, RNA Interference, Polycystic Ovary Syndrome, Adult, medicine.medical_specialty, Lipolysis, MESH: RNA Interference, Triacylglycerol lipase, Down-Regulation, Biology, Phospholipases A, MESH: Glycerol, MESH: Norepinephrine, Physiology (medical), Internal medicine, medicine, Humans, MESH: Lipolysis, Obesity, Lipase, MESH: Adipocytes, MESH: Humans, MESH: Adult, Mesenchymal Stem Cells, Sterol Esterase, MESH: Mesenchymal Stem Cells, Endocrinology, chemistry, Adipose triglyceride lipase, biology.protein, MESH: Polycystic Ovary Syndrome, MESH: Female, Hormone
Abstract: Hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) regulate adipocyte lipolysis in rodents. Objective: To compare the roles of these lipases for lipolysis in human adipocytes. Design: Subcutaneous adipose tissue was investigated. HSL and ATGL protein expression were related to lipolysis in isolated mature fat cells. ATGL or HSL were knocked down by RNA interference or selectively inhibited and effects on lipolysis studied in differentiated preadipocytes or adipocytes derived from human mesenchymal stem cells (hMSC). Setting and subjects: Outpatient investigation. Subjects were all women, 12 lean controls, 8 lean with polycystic ovary syndrome and 27 otherwise healthy obese. Results: Noradrenaline-induced lipolysis was positively correlated with HSL protein levels (P
Published: 2007

21. Involvement of cholecystokinin 2 receptor in food intake regulation: hyperphagia and increased fat deposition in cholecystokinin 2 receptor-deficient mice

Author: Claude Knauf, Rémy Burcelin, Philippe Valet, Hubert Lulka, Stéphanie Broussaud, Pascal Clerc, Maria Gràcia Coll Constans, Daniel Fourmy, Christian Carpéné, Charlotte Guigné, Catherine Seva, Luc Pénicaud, Stéphane Leung-Theung-Long, Marlène Dufresne, Christophe Perrin, Biologie et Pathologie Digestive, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Animal Facility , Institut Fédératif de Recherche 31, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Unité de recherche sur les obésités, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), 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), 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), and Simon, Marie Francoise
Subjects: Blood Glucose, Male, Mice, Obese, Cholecystokinin receptor, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Endocrinology, Glucose homeostasis, MESH: Obesity, MESH: Animals, Receptor, MESH: Mice, Obese, Adiposity, Cholecystokinin, Mice, Knockout, 2. Zero hunger, 0303 health sciences, digestive, oral, and skin physiology, MESH: Energy Metabolism, MESH: Motor Activity, Cholecystokinin B receptor, Ghrelin, MESH: Hyperphagia, medicine.drug, medicine.medical_specialty, MESH: Glucose Tolerance Test, Hyperphagia, Motor Activity, Biology, MESH: Receptor, Cholecystokinin B, 03 medical and health sciences, Insulin resistance, MESH: Mice, Inbred C57BL, Orexigenic, Internal medicine, medicine, Animals, Obesity, MESH: Mice, 030304 developmental biology, MESH: Adiposity, Appetite Regulation, Body Weight, Glucose Tolerance Test, medicine.disease, Receptor, Cholecystokinin B, MESH: Male, MESH: Body Weight, Mice, Inbred C57BL, MESH: Blood Glucose, Energy Metabolism, 030217 neurology & neurosurgery, MESH: Appetite Regulation
Abstract: International audience; The role of cholecystokinin (CCK) as a satiety factor has been extensively documented. Although most work implies that CCK1 receptor mediates the control of food intake, a contributing role for CCK2 receptor (CCK2R) in the CCK-induced satiety cannot be totally excluded. The hypothesis that CCK2R invalidation disrupts regulatory pathways with impact on feeding behavior was examined in CCK2R(-/-) mice. CCK2R(-/-) mice developed obesity that was associated with hyperphagia. Obesity was related with increased fat deposition resulting from adipocyte hypertrophy. Expression of several adipokines was dysregulated consistently with obesity. Moreover, obesity was associated with disturbed glucose homeostasis as revealed by increased fasting glycemia and insulinemia, impaired glucose tolerance, and hepatic insulin resistance in CCK2R(-/-) mice. In vitro analysis of isolated adipocytes metabolism was consistent with increased storage but preserved insulin sensitivity. Suppression of feeding and concomitant increased expression of hypothalamic proopiomelanocortin after intracerebroventricular injection of gastrin into control mice demonstrates that hypothalamic CCK2 receptors mediate inhibition of food intake. Comparative analysis of hypothalamic mediator gene expression in fed knockout and control mice demonstrated overexpression of ghrelin receptors in CCK2R(-/-) mice, indicating up-regulation of orexigenic pathways. This effect was also observed after body weight normalization, indicating a causative role in the development of hyperphagia and obesity of CCK2R(-/-) mice. Our results give evidence that CCK2 receptor activity plays a contributing regulatory role in the control of food intake.
Published: 2007

22. In vivo pharmacodynamic interactions between two drugs used in orthostatic hypotension--midodrine and dihydroergotamine

Author: Atul Pathak, Jean-Louis Montastruc, Jean-Michel Senard, Verwaerde P, Marie-Antoinette Tran, Géraldine Jourdan, Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), UP d'anesthésie-réanimation-urgences, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Pharmacocinétique et de Toxicologie clinique [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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), Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Pharmacocinétique et de Toxicologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse]
Subjects: Agonist, Male, medicine.drug_class, Midodrine, Blood Pressure, 030204 cardiovascular system & hematology, Pharmacology, Partial agonist, Dihydroergotamine, MESH: Dogs, 03 medical and health sciences, Orthostatic vital signs, Hypotension, Orthostatic, 0302 clinical medicine, Dogs, Heart Rate, medicine, Animals, MESH: Animals, Pharmacology (medical), MESH: Heart Rate, MESH: Hypotension, Orthostatic, business.industry, Antagonist, MESH: Midodrine, MESH: Blood Pressure, Drug interaction, MESH: Dihydroergotamine, MESH: Male, 3. Good health, Atropine, Anesthesia, MESH: Adrenergic alpha-Agonists, Adrenergic alpha-1 Receptor Agonists, business, Adrenergic alpha-Agonists, MESH: Receptors, Adrenergic, alpha-1, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; A combination of midodrine and dihydroergotamine (DHE) is frequently used clinically in patients suffering from severe orthostatic hypotension (OH). Whereas midodrine acts as a selective, peripheral alpha1-receptor agonist, DHE displays complex pharmacology and can behave as an alpha-adrenergic receptor agonist or antagonist. Surprisingly, the consequences of such a combination on blood pressure have never been investigated. The present study was performed in order to evaluate the pressor effects induced by the administration of both midodrine and DHE in old conscious dogs (n = 6) in experimental condition reproducing autonomic failure-related baroreflex dysfunction (atropine 0.1 mg/kg). For this purpose, we first studied the relative potency and intrinsic activity of each agonist and noradrenaline (NA) for the alpha1-adrenergic receptor. The orders of potency obtained in our study were 0.35, 11 and 400 microg/kg for NA, DHE and midodrine, and intrinsic activity: NA > midodrine > DHE. These results strongly suggest that DHE really acts in vivo as an alpha1-adrenoceptor partial agonist. Afterwards, the pressor effects of coadministration of midodrine (0.4 mg/kg) and DHE (15 microg/kg) were investigated: in one setting, midodrine was first administered, followed by DHE; in another, DHE was first administered, followed by midodrine. Our results show that in conscious dogs, the combination of midodrine and DHE leads to near-complete abolition of the pressor effect induced by the first administered drug. This in vivo proof of such antagonistic effects on blood pressure could explain clinical observations of worsening of OH in humans administered midodrine plus DHE. Although in vivo results obtained in conscious healthy dogs need to be experimentally and clinically confirmed in humans suffering from OH, these results strongly suggest that a midodrine-DHE combined treatment should be avoided in clinical practice.
Published: 2007

23. NF-kappaB is important for TNF-alpha-induced lipolysis in human adipocytes

Author: Laurencikiene, Jurga, Van Harmelen, Vanessa, Arvidsson Nordström, Elisabet, Dicker, Andrea, Blomqvist, Lennart, Näslund, Erik, Langin, Dominique, Arner, Peter, Rydén, Mikael, Simon, Marie Francoise, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Danderyds sjukhus = Danderyd University Hospital, 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), 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), Department of Surgery, Karolinska Institutet [Stockholm], 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], 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Signal Transduction, Perilipin-1, Cell Membrane Permeability, Transcription, Genetic, Lipolysis, Active Transport, Cell Nucleus, Down-Regulation, MESH: NF-kappa B, MESH: Active Transport, Cell Nucleus, MESH: Phosphoproteins, MESH: Down-Regulation, Adipocytes, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, MESH: Lipolysis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, MESH: Cell Membrane Permeability, Phosphorylation, Cells, Cultured, MESH: Adipocytes, MESH: RNA, Messenger, MESH: Humans, MESH: Phosphorylation, Tumor Necrosis Factor-alpha, MESH: Peptides, MESH: Transcription, Genetic, NF-kappa B, Phosphoproteins, MESH: Tumor Necrosis Factor-alpha, Carrier Proteins, Peptides, Signal Transduction, MESH: Cells, Cultured
Abstract: International audience; Tumor necrosis factor-alpha (TNF-alpha) promotes lipolysis in mammal adipocytes via the mitogen-activated protein kinase (MAPK) family, resulting in reduced expression/function of perilipin (PLIN). The role of another pivotal intracellular messenger activated by TNF-alpha, nuclear factor-kappaB (NF-kappaB), has not been recognized. We explored the role of NF-kappaB in TNF-alpha-induced lipolysis of human fat cells. Primary cultures of human adipocytes were incubated in the presence of a cell-permeable peptide that inhibits NF-kappaB signaling (WP). Incubation with WP, but not with a biologically inactive peptide (MP), abolished the nuclear translocation of NF-kappaB and effectively abrogated TNF-alpha-induced lipolysis in a concentration-dependent manner. Western blot analysis demonstrated that although TNF-alpha per se reduced mainly PLIN protein expression, TNF-alpha in the presence of WP resulted in a pronounced combined reduction of both hormone-sensitive lipase (HSL) and PLIN protein. The expression of a set of other lipolytic or adipocyte-specific proteins was not affected. The regulation was presumably at the transcriptional level, because mRNA expression for HSL and PLIN was markedly reduced with TNF-alpha in the presence of NF-kappaB inhibition. This was confirmed in gene reporter assays using human PLIN and HSL promoter constructs. We conclude that in the presence of NF-kappaB inhibition, TNF-alpha-mediated lipolysis is reduced, which suggests that NF-kappaB is essential for retained human fat cell lipolysis.
Published: 2007

24. Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase

Author: Pradère, Jean-Philippe, Tarnus, Evelyne, Grès, Sandra, Valet, Philippe, Saulnier-Blache, Jean Sébastien, Saulnier-Blache, Jean Sébastien, 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), 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: [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: Autotaxin (ATX) is a lysophospholipase D involved in synthesis of lysophosphatidic acid (LPA). ATX is secreted by adipocytes and is associated with adipogenesis and obesity-associated diabetes. Here we have studied the mechanisms involved in biosynthesis and secretion of ATX by mouse 3T3-F442A adipocytes. We found that inhibition of N-glycosylation with tunicamycin or by double point deletion of the amino-acids N53 and N410 of ATX inhibit its secretion. In addition, N-glycosidase treatment and point deletion of the amino-acid N410 inhibits the lysophospholipase D activity of ATX. Analysis of the amino-acid sequence of mouse ATX shows the presence of a N-terminal signal peptide. Treatment with the signal peptidase inhibitor globomycin inhibits ATX secretion by adipocytes. Transfection in Cos-7 cells of site-directed deleted ATX shows that ATX secretion is dependent on the hydrophobic core sequence of the signal peptide, not on the putative signal peptidase cleavage site sequence. Analysis of the amino-acid sequence of mouse ATX also reveals the presence of a putative cleavage site by the protein convertase furin. Treatment of adipocytes with the furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone does not modified secretion or lysophospholipase D activity of ATX. Transfection in Cos-7 cells of site-directed deleted ATX shows that the furin recognition site is not required for secretion or lysophospholipase D activity of ATX. In conclusion, the present work demonstrates the crucial role of N-glycosylation in secretion and activity of ATX. The present work also confirms the crucial role signal peptidase in secretion of ATX by adipocytes.
Published: 2007

25. Atrial natriuretic peptide inhibits the production of adipokines and cytokines linked to inflammation and insulin resistance in human subcutaneous adipose tissue

Author: Cedric Moro, Anne Bouloumié, Michel Berlan, Karine Lolmède, Dominique Langin, V. Stich, Max Lafontan, Jean Galitzky, Peter Arner, Eva Klimcakova, Simon, Marie Francoise, 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), Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-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), Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], 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), 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 pharmacologie médicale et clinique, CHU Toulouse [Toulouse], 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], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
Subjects: MESH: Inflammation, MESH: Atrial Natriuretic Factor, Endocrinology, Diabetes and Metabolism, Adipose tissue, White adipose tissue, 030204 cardiovascular system & hematology, Polymerase Chain Reaction, 0302 clinical medicine, Atrial natriuretic peptide, Abdomen, Adipocytes, Cells, Cultured, 0303 health sciences, MESH: Cytokines, MESH: Middle Aged, MESH: Adiponectin, Middle Aged, MESH: Insulin Resistance, Adipose Tissue, Cytokines, Female, Adiponectin, medicine.symptom, hormones, hormone substitutes, and hormone antagonists, MESH: Adipose Tissue, Atrial Natriuretic Factor, MESH: Cells, Cultured, Adult, medicine.medical_specialty, Adipose tissue macrophages, Adipokine, Inflammation, MESH: Abdomen, 03 medical and health sciences, Insulin resistance, MESH: RNA, Internal medicine, Internal Medicine, medicine, Lipolysis, Humans, MESH: Overweight, MESH: Adipocytes, 030304 developmental biology, MESH: Humans, business.industry, Macrophages, MESH: Macrophages, MESH: Polymerase Chain Reaction, MESH: Adult, Overweight, medicine.disease, Endocrinology, RNA, Insulin Resistance, business, MESH: Female
Abstract: International audience; AIMS/HYPOTHESIS: Increased adipose tissue secretion of adipokines and cytokines has been implicated in the chronic low-grade inflammation state and insulin resistance associated with obesity. We tested here whether the cardiovascular and metabolic hormone atrial natriuretic peptide (ANP) was able to modulate adipose tissue secretion of several adipokines (derived from adipocytes) and cytokines (derived from adipose tissue macrophages). SUBJECTS AND METHODS: We used protein array to measure the secretion of adipokines and cytokines after a 24-h culture of human subcutaneous adipose tissue pieces treated or not with a physiological concentration of ANP. The effect of ANP on protein secretion was also directly studied on isolated adipocytes and macrophages. Gene expression was measured by real-time RT-quantitative PCR. RESULTS: ANP decreased the secretion of the pro-inflammatory cytokines IL-6 and TNF-alpha, of several chemokines, and of the adipokines leptin and retinol-binding protein-4 (RBP-4). The secretion of the anti-inflammatory molecules IL-10 and adiponectin remained unaffected. The cytokines were mainly expressed in macrophages that expressed all components of the ANP-dependent signalling pathway. The adipokines, leptin, adiponectin and RBP-4 were specifically expressed in mature adipocytes. ANP directly inhibited the secretion of IL-6 and monocyte chemoattractant protein-1 by macrophages. The inhibitory effects of ANP on leptin and growth-related oncogene-alpha secretions were not seen under selective hormone-sensitive lipase inhibition. CONCLUSIONS/INTERPRETATION: We suggest that ANP, either by direct action on adipocytes and macrophages or through activation of adipocyte hormone-sensitive lipase, inhibits the secretion of factors involved in inflammation and insulin resistance.
Published: 2006

26. Dopamine beta-hydroxylase deficiency

Author: Philippe Rouet, Jean-Michel Senard, Autard, Delphine, 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), Club d'Etude du Système Nerveux Autonome, and Autonomic Unit of the Department of Clinical Pharmacology
Subjects: medicine.medical_specialty, lcsh:Medicine, Orthostatic intolerance, Dopamine beta-Hydroxylase, Review, Hypoglycemia, Autonomic Nervous System, Diagnosis, Differential, Hypotension, Orthostatic, Orthostatic vital signs, Dopamine, Internal medicine, Dopamine beta hydroxylase deficiency, medicine, Humans, Pharmacology (medical), Pure autonomic failure, Genetics (clinical), [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, lcsh:R, General Medicine, Prognosis, medicine.disease, Endocrinology, Blood pressure, Familial dysautonomia, Mutation, Deficiency Diseases, business, medicine.drug
Abstract: Dopamine beta-hydroxylase (DβH) deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS). Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.
Published: 2006

27. Beta-adrenergic and atrial natriuretic peptide interactions on human cardiovascular and metabolic regulation

Author: Christoph Schroeder, Max Lafontan, Michael Boschmann, Karsten Heusser, Cedric Moro, André Diedrich, Jens Jordan, Frauke Adams, Michel Berlan, G Franke, F. C. Luft, Jens Tank, Andreas L. Birkenfeld, Simon, Marie Francoise, Franz-Volhard Clinical Research Center, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], 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), Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine [Nashville], 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Blood Glucose, Glycerol, Male, MESH: Atrial Natriuretic Factor, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Microdialysis, Clinical Biochemistry, Fatty Acids, Nonesterified, Biochemistry, MESH: Dose-Response Relationship, Drug, Endocrinology, Atrial natriuretic peptide, Heart Rate, Infusions, Intravenous, Cells, Cultured, MESH: Fatty Acids, Nonesterified, MESH: Adrenergic beta-Antagonists, Propranolol, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Glucose, Adipose Tissue, cardiovascular system, Female, MESH: Calorimetry, Indirect, Atrial Natriuretic Factor, MESH: Adipose Tissue, medicine.drug, Blood drawing, MESH: Cells, Cultured, Adult, medicine.medical_specialty, Adrenergic beta-Antagonists, Carbohydrate metabolism, Article, Cardiovascular Physiological Phenomena, MESH: Glycerol, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Receptors, Adrenergic, beta, medicine, Humans, Muscle, Skeletal, Dose-Response Relationship, Drug, business.industry, Natriuretic peptide receptor activity, Insulin, Biochemistry (medical), MESH: Cardiovascular Physiology, Calorimetry, Indirect, MESH: Adult, Crossover study, MESH: Heart, Blood pressure, Glucose, Metabolism, MESH: Blood Glucose, business, MESH: Female
Abstract: Context: Atrial natriuretic peptide (ANP) has well-known cardiovascular effects and modifies lipid and carbohydrate metabolism in humans.Objective: The objective of the study was to determine the metabolic and cardiovascular interaction of β-adrenergic receptors and ANP.Design: This was a crossover study, conducted 2004–2005.Setting: The study was conducted at an academic clinical research center.Patients: Patients included 10 healthy young male subjects (body mass index 24 ± 1 kg/m2).Intervention: We infused iv incremental ANP doses (6.25, 12.5, and 25 ng/kg·min) with and without propranolol (0.20 mg/kg in divided doses followed by 0.033 mg/kg·h infusion). Metabolism was monitored through venous blood sampling, im, and sc microdialysis and indirect calorimetry. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings.Main Outcome Measures: Venous nonesterified fatty acid, glycerol, glucose, and insulin; and microdialysate glucose, glycerol, lactate, and pyruvate were measured.Results: ANP increased heart rate dose dependently. β-Adrenergic receptor blockade abolished the response. ANP elicited a dose-dependent increase in serum nonesterified fatty acid and glycerol concentrations. The response was not suppressed with propranolol. Venous glucose and insulin concentrations increased with ANP, both without or with propranolol. ANP induced lipid mobilization in sc adipose tissue. In skeletal muscle, microdialysate lactate increased, whereas the lactate to pyruvate ratio decreased, both with and without propranolol. Higher ANP doses increased lipid oxidation, whereas energy expenditure remained unchanged. Propranolol tended to attenuate the increase in lipid oxidation.Conclusions: Selected cardiovascular ANP effects are at least partly mediated by β-adrenergic receptor stimulation. ANP-induced changes in lipid mobilization and glycolysis are mediated by another mechanism, presumably stimulation of natriuretic peptide receptors, whereas substrate oxidation might be modulated through adrenergic mechanisms.
Published: 2006

28. Genetic polymorphisms and weight loss in obesity:a randomised trial of hypo-energetic high- versus low-fat diets

Author: Dominique Langin, Martin Nordal Petersen, Christian Dina, Oluf Pedersen, Thorkild I. A. Sørensen, Camilla Verdich, Philippe Boutin, J. Alfredo Martínez, Moira A. Taylor, Lesli H. Larsen, Claus Holst, Karine Clément, Vladimir Stich, Søren Toubro, Arne Astrup, Jean-Michel Oppert, Philippe Froguel, Peter Arner, Liselotte Petersen, Søren M. Echwald, Ian A. Macdonald, Wim H. M. Saris, Jan Polak, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), 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 - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mécanique de Lille - FRE 3723 (LML), Université de Lille, Sciences et Technologies-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), 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, Service de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de l'Hôtel-Dieu, Nutrition et obésité : approches génétique et transcriptomique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-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, Laboratoire des Amino-acides Peptides et Protéines (LAPP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre d'études spatiales de la biosphère (CESBIO), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Gestion environnementale et traitement biologique des déchets (UR GERE), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), Systèmes Macromoléculaires et Physiopathologie Humaine (SMPH), BIOMERIEUX-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Hôtel-Dieu, Department of Sport Medicine, Charles University [Prague] (CU), Section of Genomic Medicine, Imperial College London, Genome Centre, Imperial College London-Hammersmith campus, Froguel, Philippe, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Université de Lille, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel-Dieu-EA3502, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital de l'Hôtel-Dieu, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel-Dieu, Techniques of Informatics and Microelectronics for integrated systems Architecture (TIMA), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Charles University [Prague], Humane Biologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), 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), Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), 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 - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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: Candidate gene, MESH: Diabetes Mellitus, MESH: Pedigree, media_common.quotation_subject, Adipokine, Physiology, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: Insulin-Secreting Cells, 03 medical and health sciences, 0302 clinical medicine, Weight loss, MESH: Receptors, Drug, MESH: Hypoglycemic Agents, Medicine, MESH: Tolbutamide, Pharmacology (medical), Gene–environment interaction, MESH: Birth Weight, Nutrition, 030304 developmental biology, media_common, MESH: Heterozygote, 2. Zero hunger, Genetics, 0303 health sciences, MESH: Mutation, Missense, MESH: Humans, business.industry, Haplotype, MESH: Infant, Newborn, MESH: Potassium Channels, Inwardly Rectifying, Appetite, General Medicine, MESH: Potassium Channels, medicine.disease, Obesity, MESH: Male, 3. Good health, MESH: Diabetes Complications, MESH: Developmental Disabilities, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: ATP-Binding Cassette Transporters, medicine.symptom, business, MESH: Female, MESH: Sulfonylurea Compounds, Research Article
Abstract: Objectives: To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet. Design: Randomised, parallel, two-arm, open-label multi-centre trial. Setting: Eight clinical centres in seven European countries. Participants: 771 obese adult individuals. Interventions: 10-wk dietary intervention to hypo-energetic (−600 kcal/d) diets with a targeted fat energy of 20%–25% or 40%–45%, completed in 648 participants. Outcome Measures: WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants. Results: Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from −0.6 to 0.8 kg, and homozygotes, from −0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to −1.6 kg in heterozygotes, and from 3.8 kg to −2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant. Conclusions: Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet., Editorial Commentary Background: Obesity is an important cause of death and disease, particularly in the developed world. It is understood that both environmental and genetic factors contribute towards obesity. Numerous studies have associated particular gene variants with a tendency towards obesity, but it is not known whether such gene variants affect the degree to which obese individuals will lose weight when dieting. What this trial shows: As part of a randomised trial, 771 participants were assigned to one of two different low-energy diets for 10 weeks: one low in fat or one high in fat. The researchers then did a genetic analysis of 642 participants completing the intervention, to find out whether any of 42 distinct genetic variations in 26 genes were associated with weight loss in the trial. The genetic variants were chosen for study as they were known or already thought to be associated with appetite regulation or various aspects of metabolism and fat tissue development and function. The investigators found that none of the genetic variants studied had a significant association with weight loss in the trial. It was also seen that the majority of genetic variants were not associated with efficacy of one dietary intervention over another. Strengths and limitations: Although a large number of participants was recruited into the trial, the genetic analysis involved multiple comparisons—168 tests of 42 genetic variants. This increases the likelihood that any significant associations found could have resulted from chance alone. Significant associations from this study will require additional confirmation in larger studies. Contribution to the evidence: This study adds data indicating that variation in the genes studied did not have an important influence on weight loss.
Published: 2006

29. Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development

Author: Jos Jonkers, Marga A. van Rooijen, Michael J.O. Wakelam, Jean Philippe Pradère, Jean Sébastien Saulnier-Blache, Paula Ruurs, Trevor R. Pettit, Laurens A. van Meeteren, Peter Bouwman, Christine L. Mummery, Wouter H. Moolenaar, Catelijne Stortelers, Saulnier-Blache, Jean Sébastien, Division of Cellular Biochemistry and Center for biomedical Genetics, The Netherlands Cancer Institute, Division of Molecular Biology, Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 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), CRUK Institute for Cancer Studies, and University of Alabama at Birmingham [ Birmingham] (UAB)
Subjects: Angiogenesis, MESH: Pyrophosphatases, MESH: GTP-Binding Protein alpha Subunits, G12-G13, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Multienzyme Complexes, GTP-Binding Protein alpha Subunits, G12-G13, MESH: Mice, Knockout, MESH: Lysophospholipids, MESH: Phosphodiesterase I, chemistry.chemical_compound, Mice, Multienzyme Complexes, Lysophosphatidic acid, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Animals, MESH: Animals, Yolk sac, Pyrophosphatases, Receptors, Lysophosphatidic Acid, Receptor, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, [SDV.BDD]Life Sciences [q-bio]/Development Biology, LPAR3, Mice, Knockout, LPAR1, Phosphoric Diester Hydrolases, MESH: Embryo, Cell migration, Cell Biology, Articles, MESH: Blood Vessels, Embryo, Mammalian, Cell biology, medicine.anatomical_structure, chemistry, Biochemistry, Phosphodiesterase I, Blood Vessels, Genes, Lethal, lipids (amino acids, peptides, and proteins), MESH: Genes, Lethal, Autotaxin, Lysophospholipids, MESH: Phosphoric Diester Hydrolases, MESH: Receptors, Lysophosphatidic A
Abstract: Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that promotes cell migration, metastasis, and angiogenesis. ATX generates lysophosphatidic acid (LPA), a lipid mitogen and motility factor that acts on several G protein-coupled receptors. Here we report that ATX-deficient mice die at embryonic day 9.5 (E9.5) with profound vascular defects in yolk sac and embryo resembling the Galpha13 knockout phenotype. Furthermore, at E8.5, ATX-deficient embryos showed allantois malformation, neural tube defects, and asymmetric headfolds. The onset of these abnormalities coincided with increased expression of ATX and LPA receptors in normal embryos. ATX heterozygous mice appear healthy but show half-normal ATX activity and plasma LPA levels. Our results reveal a critical role for ATX in vascular development, indicate that ATX is the major LPA-producing enzyme in vivo, and suggest that the vascular defects in ATX-deficient embryos may be explained by loss of LPA signaling through Galpha13.
Published: 2006

30. [Secretion and role of autotaxin and lysophosphatidic acid in adipose tissue]

Author: Jean Sébastien, Saulnier-Blache, 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), and Saulnier-Blache, Jean Sébastien
Subjects: MESH: Pyrophosphatases, MESH: Receptors, G-Protein-Coupled, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Multienzyme Complexes, Receptors, G-Protein-Coupled, MESH: Lysophospholipids, MESH: Phosphodiesterase I, Multienzyme Complexes, Adipocytes, Homeostasis, Humans, MESH: Obesity, Obesity, Pyrophosphatases, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Adipocytes, MESH: Humans, Phosphoric Diester Hydrolases, Adipose Tissue, Diabetes Mellitus, Type 2, Phosphodiesterase I, MESH: Homeostasis, MESH: Cell Division, lipids (amino acids, peptides, and proteins), Lysophospholipids, MESH: Phosphoric Diester Hydrolases, Cell Division, MESH: Adipose Tissue, MESH: Diabetes Mellitus, Type 2
Abstract: International audience; In obesity, adipocyte hypertrophy is often associated with recrutement of new fat cells (adipogenesis) under the control of circulating and local regulatory factors. Among the different lipids released in the extracellular compartment of adipocytes, our group found the presence of lysophosphatidic acid (LPA). LPA is a bioactive phospholipid able to regulate several cell responses via the activation of specific G-protein coupled membrane receptors. Our group found that LPA increases preadipocyte proliferation and inhibits adipogenesis via the activation of LPA1 receptor subtype. Extracellular LPA-synthesis is catalyzed by a lysophospholipase D secreted by adipocytes: autotaxin (ATX). Adipocyte ATX expression strongly increases with adipogenesis as well as in individuals exhibiting type 2 diabetes associated with massive obesity. A possible contribution of ATX and LPA as paracrine regulators of adipogenesis and obesity associated diabetes is proposed.
Published: 2006

31. Lysophosphatidic acid inhibits adipocyte differentiation via lysophosphatidic acid 1 receptor-dependent down-regulation of peroxisome proliferator-activated receptor gamma2

Author: Jerold Chun, Jean Sébastien Saulnier-Blache, Philippe Valet, Marie Simon, Martin Wabitsch, Danièle Daviaud, Charlotte Guigné, Jean Philippe Pradère, Sandra Grès, 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), Department of Pediatrics, Universität Ulm - Ulm University [Ulm, Allemagne], Department of Molecular Biology, The Scripps Research Institute [La Jolla, San Diego], and Saulnier-Blache, Jean Sébastien
Subjects: Male, Time Factors, MESH: 3T3 Cells, Transcription, Genetic, Oligonucleotides, Peroxisome proliferator-activated receptor, Adipose tissue, Biochemistry, MESH: Down-Regulation, Culture Media, Serum-Free, Monocytes, chemistry.chemical_compound, Mice, Adipocyte, Lysophosphatidic acid, Adipocytes, MESH: Animals, Pyrophosphatases, Receptor, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, chemistry.chemical_classification, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Cell Differentiation, 3T3 Cells, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Culture Media, Serum-Free, Adipose Tissue, Adipogenesis, Phosphodiesterase I, lipids (amino acids, peptides, and proteins), Phosphoenolpyruvate Carboxykinase (GTP), biological phenomena, cell phenomena, and immunity, Autotaxin, MESH: Adipose Tissue, MESH: Cell Differentiation, medicine.medical_specialty, Blotting, Western, MESH: Glycoproteins, Down-Regulation, MESH: Carrier Proteins, Mice, Transgenic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Fatty Acid-Binding Proteins, MESH: Fatty Acid-Binding Proteins, Cell Line, Rosiglitazone, Downregulation and upregulation, Multienzyme Complexes, MESH: Cell Proliferation, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, MESH: Blotting, Western, Animals, Humans, Hypoglycemic Agents, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, MESH: Adipocytes, Triglycerides, Cell Proliferation, Glycoproteins, MESH: Hu, Phosphoric Diester Hydrolases, Glucose-6-Phosphate Isomerase, Cell Biology, MESH: Cell Line, PPAR gamma, Endocrinology, chemistry, RNA, Thiazolidinediones, Lysophospholipids, Carrier Proteins, MESH: Autocrine Motility Factor
Abstract: Lysophosphatidic acid (LPA) is a bioactive phospholipid acting via specific G protein-coupled receptors that is synthesized at the extracellular face of adipocytes by a secreted lysophospholipase D (autotaxin). Preadipocytes mainly express the LPA(1) receptor subtype, and LPA increases their proliferation. In monocytes and CV1 cells LPA was recently reported to bind and activate peroxisome proliferator-activated receptor gamma (PPARgamma), a transcription factor also known to play a pivotal role in adipogenesis. Here we show that, unlike the PPARgamma agonist rosiglitazone, LPA was unable to increase transcription of PPARgamma-sensitive genes (PEPCK and ALBP) in the mouse preadipose cell line 3T3F442A. In contrast, treatment with LPA decreased PPARgamma2 expression, impaired the response of PPARgamma-sensitive genes to rosiglitazone, reduced triglyceride accumulation, and reduced the expression of adipocyte mRNA markers. The anti-adipogenic activity of LPA was also observed in the human SGBS (Simpson-Golabi-Behmel syndrome) preadipocyte cell line, as well as in primary preadipocytes isolated from wild type mice. Conversely, the anti-adipogenic activity of LPA was not observed in primary preadipocytes from LPA(1) receptor knock-out mice, which, in parallel, exhibited a higher adiposity than wild type mice. In conclusion, LPA does not behave as a potent PPARgamma agonist in adipocytes but, conversely, inhibits PPARgamma expression and adipogenesis via LPA(1) receptor activation. The local production of LPA may exert a tonic inhibitory effect on the development of adipose tissue.
Published: 2005

32. Acide lysophosphatidique : un nouveau lien entre plaquettes sanguines et métastases osseuses

Author: Philippe Clézardin, Ahmed Boucharaba, Olivier Peyruchaud, Jean-Sébastien Saulnier-Blache, Saulnier-Blache, Jean Sébastien, Mecanismes et Traitements des Metastases Osseuses des Tumeurs Solides, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Humans, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, MESH: Bone Neoplasms, MESH: Research Support, Non-U.S. Gov't, General Biochemistry, Genetics and Molecular Biology, MESH: Lysophospholipids, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Animals, MESH: Blood Platelets
Abstract: La formation de metastases osseuses est une complication frequente au cours du developpement de nombreux cancers (sein, prostate, foie, reins, thyroide). Les metastases osseuses sont souvent associees a une degradation du tissu osseux qui est a l’origine de douleurs intenses, d’une elevation de la calcemie et de fractures pathologiques. Ces metastases sont en general tres invalidantes et liees a une tres forte morbidite [1]. Dans le cas du cancer du sein, les donnees cliniques et experimentales actuelles indiquent que les cellules tumorales presentent dans la cavite medullaire produisent un certain nombre de facteurs proteine apparentee a la parathormone (PTHrP), cytokines qui stimulent l’activite des osteoclastes dont la principale fonction est de degrader l’os. Le tissu osseux etant un reservoir de facteurs de croissance tels que le transforming growth factor beta (TGFbeta) et les insulin like growth factors (IGF) [2], ces facteurs de croissance sont liberes de la matrice osseuse au cours de la resorption ; ils vont alors stimuler le developpement des cellules tumorales ainsi que la production de PTHrP par ces cellules, ce qui va amplifier l’activite de resorption des osteoclastes. La metastase osseuse est alors le siege d’un cercle vicieux dans lequel la resorption osseuse et le developpement tumoral s’entretiennent mutuellement [3]. Les traitements actuels des patients ayant des metastases osseuses, utilisant des inhibiteurs puissants de la resorption osseuse (bisphosphonates), permettent de ralentir la progression de
Published: 2005

33. Les peptides natriurétiques : une nouvelle voie de régulation de la lipolyse chez l'homme

Author: Sengenes, Coralie, Moro, Cédric, Galitzky, Jean, Berlan, Michel, Lafontan, Max, Maylin, Françoise, 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), 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: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Humans, MESH: Atrial Natriuretic Factor, MESH: Natriuretic Agents, MESH: Lipolysis, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Brain-Derived Neurotrophic Factor, MESH: English Abstract, MESH: Adipocytes, MESH: Adipose Tissue
Abstract: Human fat cell lipolysis was considered until recently to be an exclusive cAMP/protein-kinase A (PKA)-regulated metabolic pathway under the control of catecholamines and insulin. Moreover, exercise-induced lipid mobilization in humans was considered to mainly depend on catecholamine action and interplay between fat cell beta- and alpha2-adrenergic receptors controlling adenylyl cyclase activity and cAMP production. We have recently demonstrated that natriuretic peptides stimulate lipolysis and contribute to the regulation of lipid mobilization in humans. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) stimulate lipolysis in human isolated fat cells. Activation of the adipocyte plasma membrane type A guanylyl cyclase receptor (NPR-A), increase in intracellular guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels and activation of hormone-sensitive lipase mediate the action of ANP. ANP does not modulate cAMP production and PKA activity. Increment of cGMP induces the phosphorylation of hormone-sensitive lipase and perilipin A via the activation of a cGMP dependent protein kinase-I (cGK-I). Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans. Physiological relevance of the ANP-dependent pathway was demonstrated in young subjects performing physical exercise. ANP plays a role in conjunction with catecholamines in the control of exercise-induced lipid mobilization. This pathway becomes of major importance when subjects are submitted to chronic treatment with a beta-blocker. Oral beta-adrenoceptor blockade suppresses the beta-adrenergic component of catecholamine action in fat cells and potentiates exercise-induced ANP release by the heart. These findings may have several implications whenever natriuretic peptide secretion is altered such as in subjects with left ventricular dysfunction, congestive heart failure and obesity.
Published: 2005

34. Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression

Author: Christian Carpéné, Philippe Valet, Charlotte Guigné, J. P. Pradères, Didier Quilliot, Gilles Ferry, Jean A. Boutin, Jean Sébastien Saulnier-Blache, Marie-Françoise Simon, Jeremie Boucher, D. Prévot, Sandra Grès, Saulnier-Blache, Jean Sébastien, 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), Service de Diabétologie, Nutrition et Maladies métaboliques [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche de Croissy, Institut de Recherche Servier, 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Endocrinology, Diabetes and Metabolism, Glucose uptake, medicine.medical_treatment, Adipose tissue, Impaired glucose tolerance, Mice, chemistry.chemical_compound, 0302 clinical medicine, Adipocyte, Adipocytes, MESH: Diabetes Mellitus, Experimental, MESH: Animals, Pyrophosphatases, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, MESH: Gene Expression Regulation, Enzymologic, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Gene Expression Regulation, MESH: Insulin Resistance, Phosphodiesterase I, 030220 oncology & carcinogenesis, lipids (amino acids, peptides, and proteins), Autotaxin, Rosiglitazone, medicine.drug, MESH: Diabetes Mellitus, Type 2, medicine.medical_specialty, MESH: Biological Transport, MESH: Glycoproteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Deoxyglucose, Biology, Gene Expression Regulation, Enzymologic, Article, Diabetes Mellitus, Experimental, 03 medical and health sciences, Insulin resistance, Lipectomy, Multienzyme Complexes, Internal medicine, Internal Medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Adipocytes, Glycoproteins, 030304 developmental biology, MESH: Humans, Phosphoric Diester Hydrolases, Insulin, Glucose-6-Phosphate Isomerase, Biological Transport, medicine.disease, MESH: Deoxyglucose, Mice, Inbred C57BL, Endocrinology, Diabetes Mellitus, Type 2, Gene Expression Regulation, chemistry, Insulin Resistance, MESH: Autocrine Motility Factor
Abstract: AIMS/HYPOTHESIS: Autotaxin is a lysophospholipase D that is secreted by adipocytes and whose expression is substantially up-regulated in obese, diabetic db/db mice. The aim of the present study was to depict the physiopathological and cellular mechanisms involved in regulation of adipocyte autotaxin expression. METHODS: Autotaxin mRNAs were quantified in adipose tissue from db/db mice (obese and highly diabetic type 2), gold-thioglucose-treated (GTG) mice (highly obese and moderately diabetic type 2), high-fat diet-fed (HFD) mice (obese and moderately diabetic type 2), streptozotocin-treated mice (thin and diabetic type 1), and massively obese humans with glucose intolerance. RESULTS: When compared to non-obese controls, autotaxin expression in db/db mice was significantly increased, but not in GTG, HFD, or streptozotocin-treated mice. During db/db mice development, up-regulation of autotaxin occurred only 3 weeks after the emergence of hyperinsulinaemia, and simultaneously with the emergence of hyperglycaaemia. Adipocytes from db/db mice exhibited a stronger impairment of insulin-stimulated glucose uptake than non-obese and HFD-induced obese mice. Autotaxin expression was up-regulated by treatment with TNFalpha (insulin resistance-promoting cytokine), and down-regulated by rosiglitazone treatment (insulin-sensitising compound) in 3T3F442A adipocytes. Finally, adipose tissue autotaxin expression was significantly up-regulated in patients exhibiting both insulin resistance and impaired glucose tolerance. CONCLUSIONS/INTERPRETATION: The present work demonstrates the existence of a db/db-specific up-regulation of adipocyte autotaxin expression, which could be related to the severe type 2 diabetes phenotype and adipocyte insulin resistance, rather than excess adiposity in itself. It also showed that type 2 diabetes in humans is also associated with up-regulation of adipocyte autotaxin expression.
Published: 2005

35. [Lysophosphatidic acid: a 'bioactive' phospholipid]

Author: Saulnier-Blache, Jean-Sébastien, Saulnier-Blache, Jean Sébastien, 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), 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: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Humans, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Lysophospholipids, MESH: Disease, MESH: Receptors, Lysophosphatidic Acid, Animals, Humans, lipids (amino acids, peptides, and proteins), MESH: Animals, Disease, biological phenomena, cell phenomena, and immunity, Lysophospholipids, Receptors, Lysophosphatidic Acid, MESH: English Abstract, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: Lysophosphatidic acid (LPA) is a "bioactive" phospholipid able to generate growth factor-like activities in a wide variety of normal and malignant cell types. LPA is proposed to play an important role in normal physiological situations such as wound healing, vascular tone, vascular integrity, or reproduction. In parallel, LPA could also be involved in the etiology of some diseases such as atherosclerosis, cancer, or obesity. The bioactivity of LPA is mediated by the activation of specific G-protein coupled receptors (LPA1, LPA2, and LPA3) leading to the activation of a number of intracellular effectors. LPA is present in solution (bound to albumin) in various extracellular fluids (blood, ascites, aqueous humor), and is released in vitro by some cell types such as platelets, cancer cells, or adipocytes. LPA is a rather polar phospholipid, which cannot easily diffuse throughout plasma membrane, and its presence outside the cells requires soluble phospholipases (secreted phospholipase A2 and soluble lysophospholipase D/autotaxin), which synthesize LPA directly in the extracellular milieu, from precursors such as phosphatidic acid and lysophosphatidylcholine. In the future, LPA receptors, as well as the enzymes involved in LPA metabolism, will constitute promising pharmacological and transgenic targets to determine the physiopathological relevance of "bioactive" LPA in vivo.
Published: 2004

36. CARDIAC VEGETATIVE NERVOUS SYSTEM AND TRANSCRIPTOME MODIFICATIONS IN OBESITY

Author: Philip-Couderc, Pierre, Philip-Couderc, Pierre, 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), Université Paul Sabatier - Toulouse III, and Philippe Rouet(pierre.philip-couderc@medecine.unige.ch)
Subjects: Obesité-Cardiopathies-profil d'expression genique, Obesity-Cardiopathy-gene expression profile, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract: The prevalence of obesity follows a progression without precedent in the industrialized countries and increases the cardiovascular morbimortality dramatically. The excessive development of adipocyte has a direct impact on heart through peptides and cytokines which it secretes and an indirect impact through the increase in the volemy. These changes induce modifications of the gene expression in the cardiomyocytes and fibroblasts. For example, the expression of the muscarinic M2 receptor decreases in the right atria from obese and hypertensive dogs.In this canine model, we showed in the M2/eNOS pathway that there were compensatory regulations at the level of the eNOS. We also showed that the adrenomedullin, peptide implied in pressure homeostasis and secreted by adipocytes, determines the compensatory surexpression of the M2 receptor, in the model of P19 cardiomyocytes lines.We undertook a general study on the level of the transcriptome with the aim to identify the whole of the modifications induced in the obese heart. These studies, in the model of hypertensive obese dog, then at Man showed that the heart of obese modified the expression of its genes and that it had a particular transcriptional profile. These regulations converge towards TGF beta and Wnt pathways, both normally implied in the cardiogenesis. Lastly, this work initiated the unknown new gene study (PPR1 & PPR2)., La prévalence de l'obésité suit une progression sans précédent dans les pays industrialisés et augmente dramatiquement la morbimortalité cardiovasculaire. Le développement excessif du tissu adipeux a un impact direct sur le tissu myocardique au travers des peptides et cytokines qu'il sécrète et un impact indirect au travers de l'augmentation de la volémie. Ces changements induisent des modifications de l'expression génique dans les cardiomyocytes et les fibroblastes cardiaques. Par exemple, l'expression du récepteur M2 diminue dans l'OD de chiens rendus obèses hypertendus.Dans ce modèle canin, nous avons montré dans la voie M2/eNOS qu'il existait des régulations compensatoires au niveau de la eNOS. Nous avons également montré que l'adrénomedulline, peptide impliqué dans l'homéostasie tensionnelle et sécrété par le tissu adipeux, détermine la surexpression compensatoire du récepteur M2, dans le modèle de cardiomyocytes de la lignée P19.Nous avons entrepris une étude globale au niveau du transcriptome dans le but d'identifier l'ensemble des modifications induites dans le cœur de l'obèse. Ces études, dans le modèle de chien obèse hypertendu, puis chez l'Homme ont montré que le cœur de l'obèse modifiait très précocement l'expression de ses gènes et qu'il avait un profil transcriptionnel unique. Ces régulations convergent notamment vers la voie TGF Β et la voie Wnt, toutes deux normalement impliquées dans la cardiogénèse. Enfin, ces travaux ont initié l'étude de gènes nouveaux inconnus (PPR1 & PPR2).
Published: 2004

37. Comparison of potassium measurement in whole blood and plasma of horse, cow, and sheep with the Reflovet® Plus system

Author: Diquélou, Armelle, Gourdin, Julien, Médaille, Christine, Verwaerde, Patrick, Trumel, Catherine, Braun, Jean-Pierre, Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Vebiotel - Laboratoire de Biologie Vétérinaire, Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Physiopathologie et Toxicologie Expérimentales (UPTE), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], mouton, potassium, [SDV]Life Sciences [q-bio], vache, sang total, cheval, plasma
Abstract: International audience; Le système d’analyses biochimiques Reflovet® Plus est fondé sur l’utilisation de bandelettes réactives pour analyse du sang total, excepté pour la mesure du potassium. Cette recommandation repose sur l’interférence possible du potassium libéré par les érythrocytes. La faible concentration en potassium dans les érythrocytes de certaines espèces animales suggère la possibilité d’utiliser du sang total. Cette possibilité a été étudiée en comparant les résultats obtenus dans 98, 102, 98 spécimens de sang total (Sg) et de plasma (P) chez le cheval, la vache et le mouton. Chez le cheval et la vache, les différences étaient faibles (respectivement 0,10 et 0,15 mmol/L), les équations des régressions de Passing-Bablock étaient respectivement Sg-Potassium = 0.875 • P-Potassium + 0.307, et Sg-Potassium = 1.036 • PPotassium - 0.325. Chez le mouton, la concordance ente les deux séries de mesure était moins bonne ; la différence moyenne était de 0.43 mmol/L et la régression correspondante : Sg-Potassium = 1.512 • P-Potassium - 2.306. Les effets de l’hématocrite et de l’hémolyse sur la différence entre mesures dans le sang total et le plasma ont été modérés. D’un point de vue pratique, les bandelettes réactives potassium peuvent être utilisées avec le sang total chez le cheval et la vache, mais non chez le mouton.
Published: 2004

38. HTLV-1 and -2 envelope SU subdomains and critical determinants in receptor binding

Author: Kim, F. J., Manel, N., Garrido, E. N., Valle, C., Marc Sitbon, Battini, J. L., Adele, Sarah, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: lcsh:Immunologic diseases. Allergy, Human T-lymphotropic virus 1, Protein Folding, Binding Sites, Research, viruses, Human T-lymphotropic virus 2, Restriction Mapping, virus diseases, Membrane Fusion, Peptide Fragments, Cell Fusion, Viral Envelope Proteins, hemic and lymphatic diseases, Virus/chemistry/*physiology Restriction Mapping Viral Envelope Proteins/chemistry/*physiology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Receptors, Virus, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Amino Acid Sequence Binding Sites Cell Fusion Conserved Sequence Human T-lymphotropic virus 1/*physiology Human T-lymphotropic virus 2/*physiology Humans Membrane Fusion Peptide Fragments Protein Folding Receptors, lcsh:RC581-607, Conserved Sequence
Abstract: Background Human T-cell leukemia virus (HTLV) -1 and -2 are deltaretroviruses that infect a wide range of cells. Glut1, the major vertebrate glucose transporter, has been shown to be the HTLV Env receptor. While it is well established that the extracellular surface component (SU) of the HTLV envelope glycoprotein (Env) harbors all of the determinants of interaction with the receptor, identification of SU subdomains that are necessary and sufficient for interaction with the receptor, as well as critical amino acids therein, remain to be precisely defined. Although highly divergent in the rest of their genomes, HTLV and murine leukemia virus (MLV) Env appear to be related and based on homologous motifs between the HTLV and MLV SU, we derived chimeric HTLV/MLV Env and soluble HTLV-1 and -2 truncated amino terminal SU subdomains. Results Using these SU constructs, we found that the 183 and 178 amino terminal residues of the HTLV-1 and -2 Env, respectively, were sufficient to efficiently bind target cells of different species. Binding resulted from bona fide interaction with the HTLV receptor as isolated SU subdomains specifically interfered with HTLV Env-mediated binding, cell fusion, and cell-free as well as cell-to-cell infection. Therefore, the HTLV receptor-binding domain (RBD) lies in the amino terminus of the SU, immediately upstream of a central immunodominant proline rich region (Env residues 180 to 205), that we show to be dispensible for receptor-binding and interference. Moreover, we identified a highly conserved tyrosine residue at position 114 of HTLV-1 Env, Tyr114, as critical for receptor-binding and subsequent interference to cell-to-cell fusion and infection. Finally, we observed that residues in the vicinity of Tyr114 have lesser impact on receptor binding and had various efficiency in interference to post-binding events. Conclusions The first 160 residues of the HTLV-1 and -2 mature cleaved SU fold as autonomous domains that contain all the determinants required for binding the HTLV receptor.
Published: 2004

39. Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity

Author: Ferry, Gilles, Tellier, Edwige, Try, Anne, Grés, Sandra, Naime, Isabelle, Simon, Marie Françoise, Rodriguez, Marianne, Boucher, Jérémie, Tack, Ivan, Gesta, Stéphane, Chomarat, Pascale, Dieu, Marc, Raes, Martine, Galizzi, Jean Pierre, Valet, Philippe, Boutin, Jean, Saulnier-Blache, Jean Sébastien, Centre de Recherche de Croissy, Institut de Recherche Servier, 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), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), 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), Pharmacologie Moleculaire et Physiopathologie Renale, Université de Namur [Namur] (UNamur), 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), Saulnier-Blache, Jean Sébastien, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH: Cell Differentiation, DNA, Complementary, Time Factors, Molecular Sequence Data, MESH: Glycoproteins, MESH: Amino Acid Sequence, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Transfection, Article, Mass Spectrometry, MESH: Databases, Mice, Multienzyme Complexes, Adipocytes, Animals, MESH: Cloning, Molecular, MESH: Animals, Amino Acid Sequence, RNA, Messenger, Cloning, Molecular, Pyrophosphatases, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Adipocytes, Glycoproteins, MESH: Culture Media, Conditioned, Phosphoric Diester Hydrolases, Reverse Transcriptase Polymerase Chain Reaction, Glucose-6-Phosphate Isomerase, MESH: Lysopho, Cell Differentiation, MESH: DNA, Complementary, Recombinant Proteins, Up-Regulation, Mice, Inbred C57BL, MESH: COS Cells, Databases as Topic, Phosphodiesterase I, Culture Media, Conditioned, COS Cells, RNA, MESH: Cell Division, Electrophoresis, Polyacrylamide Gel, Lysophospholipids, Cell Division, MESH: Electrophoresis, Polyacrylamide Gel, MESH: Autocrine Motility Factor
Abstract: Our group has recently demonstrated (Gesta, S., Simon, M., Rey, A., Sibrac, D., Girard, A., Lafontan, M., Valet, P., and Saulnier-Blache, J. S. (2002) J. Lipid Res. 43, 904-910) the presence, in adipocyte conditioned-medium, of a soluble lysophospholipase d-activity (LPLDact) involved in synthesis of the bioactive phospholipid lysophosphatidic acid (LPA). In the present report, LPLDact was purified from 3T3F442A adipocyte-conditioned medium and identified as the type II ecto-nucleotide pyrophosphatase phosphodiesterase, autotaxin (ATX). A unique ATX cDNA was cloned from 3T3F442A adipocytes, and its recombinant expression in COS-7 cells led to extracellular release of LPLDact. ATX mRNA expression was highly up-regulated during adipocyte differentiation of 3T3F442A-preadipocytes. This up-regulation was paralleled by the ability of newly differentiated adipocytes to release LPLDact and LPA. Differentiation-dependent up-regulation of ATX expression was also observed in a primary culture of mouse preadipocytes. Treatment of 3T3F442A-preadipocytes with concentrated conditioned medium from ATX-expressing COS-7 cells led to an increase in cell number as compared with concentrated conditioned medium from ATX non-expressing COS-7 cells. The specific effect of ATX on preadipocyte proliferation was completely suppressed by co-treatment with a LPA-hydrolyzing phospholipase, phospholipase B. Finally, ATX expression was found in mature adipocytes isolated from mouse adipose tissue and was substantially increased in genetically obese-diabetic db/db mice when compared with their lean siblings. In conclusion, the present work shows that ATX is responsible for the LPLDact released by adipocytes and exerts a paracrine control on preadipocyte growth via an LPA-dependent mechanism. Up-regulations of ATX expression with adipocyte differentiation and genetic obesity suggest a possible involvement of this released protein in the development of adipose tissue and obesity-associated pathologies.
Published: 2003

40. Culture of human adipose tissue explants leads to profound alteration of adipocyte gene expression

Author: Philippe Valet, Danièle Daviaud, Anne Bouloumié, Jean-Sébastien Saulnier-Blache, Stephane Gesta, Max Lafontan, Michel Berlan, Karine Lolmède, Saulnier-Blache, Jean Sébastien, 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), Biologie de l'adipocyte, physiologie du tissu adipeux et obésités, 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: Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, Gene Expression, Receptors, Cytoplasmic and Nuclear, Biochemistry, chemistry.chemical_compound, Endocrinology, Adipocyte, 1-Methyl-3-isobutylxanthine, Gene expression, Adipocytes, Lipoprotein lipase, Glucose Transporter Type 1, MESH: 1-Methyl-3-isobutylxanthine, Nuclear Proteins, General Medicine, MESH: Glucose Transporter T, Middle Aged, Neoplasm Proteins, DNA-Binding Proteins, Adipose Tissue, Female, Hypoxia-Inducible Factor 1, Fatty Acid-Binding Protein 7, MESH: Forskolin, Glycolysis, MESH: Adipose Tissue, Adult, medicine.medical_specialty, MESH: Gene Expression, Monosaccharide Transport Proteins, Lipolysis, Peroxisome Proliferation, MESH: Carrier Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Fatty Acid-Binding Proteins, MESH: Actins, MESH: Fatty Acid-Binding Proteins, Internal medicine, Culture Techniques, medicine, Humans, RNA, Messenger, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Adipocytes, Tumor Necrosis Factor-alpha, Tumor Suppressor Proteins, Biochemistry (medical), Colforsin, MESH: Adult, Sterol Esterase, Hypoxia-Inducible Factor 1, alpha Subunit, Actins, Culture Media, Lipoprotein Lipase, chemistry, MESH: Culture Techniques, Anaerobic glycolysis, MESH: Culture Media, MESH: Cholesterol Esterase, Carrier Proteins, MESH: Female, MESH: DNA-Binding Proteins, Explant culture, Transcription Factors
Abstract: Primary culture of adipose tissue has often been used to investigate pharmacological and nutritional regulation of adipocyte gene expression. Possible alteration of adipocyte gene expression by primary culture on its own has not been explored in detail. In order to address this issue, explants were prepared from human subcutaneous adipose tissue recovered from plastic surgery and maintained for 0 to 48 h in DMEM supplemented with 10 % serum. At different time points, adipocytes were isolated from the explants by collagenase digestion, and mRNA expression and lipolysis were studied. Culture was associated with an accumulation of tumor necrosis factor-alpha (TNFalpha) in the culture medium, an increase in anaerobic glycolysis, and an increase in the basal lipolysis. In parallel, a rapid and dramatic decrease in the level of mRNA encoding for several adipocyte-specific proteins such as adipocyte lipid-binding protein, hormone-sensitive lipase, lipoprotein lipase, and peroxisome proliferation activating receptor-gamma2 was observed in isolated adipocytes. These downregulations were reminiscent of a dedifferentiation process. In parallel, primary culture was associated with an increase in adipocyte beta-actin, TNFalpha, glucose transporter-1 and hypoxia-induced factor-1alpha mRNAs. Treatment of explants with agents that increase cAMP (isobutylmethylxanthine and forskolin) prevented TNFalpha production and expression and culture-induced alterations of adipocyte gene expression. These data show that primary culture of human adipose tissue explants dramatically alters adipocyte gene expression.
Published: 2003

41. Identification of an HTLV envelope receptor and its impact on cell physiology

Author: Manel, N., Kim, Fj, Kinet, S., Valle, C., Wieckowski, S., Taylor, N., Marc Sitbon, Battini, J., Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Adele, Sarah
Subjects: [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Published: 2003

42. Effect of prolonged treatment with tyramine on glucose tolerance in streptozotocin-induced diabetic rats

Author: Nicolas Morin, P Marq, Caroline Subra, Christian Carpéné, Françoise Nepveu, V. Visentin, D. Prévot, Philippe Valet, Sandy Bour, Marie-Carmen Monje, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut de Recherche pour le Développement - IRD (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), Pharmacochimie et Biologie pour le Développement - PHARMA-DEV (Toulouse, France), Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), 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), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)
Subjects: Blood Glucose, Male, medicine.medical_specialty, Semicarbazide-sensitive amine oxidase, Physiology, Monoamine oxidase, Glucose uptake, medicine.medical_treatment, Tyramine, Biochemistry, Diabetes Mellitus, Experimental, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Internal medicine, Diabetes mellitus, Biogenic amine, Adipocytes, medicine, Animals, Génie chimique, Insulin, Rats, Wistar, Génie des procédés, Infusion Pumps, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Chemistry, Diabetes, Glucose transporter, General Medicine, Glucose Tolerance Test, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Streptozotocin, 3. Good health, Rats, Glucose, Endocrinology, 030220 oncology & carcinogenesis, Vanadates, Injections, Intraperitoneal, medicine.drug
Abstract: International audience; The biogenic amine tyramine has been reported to stimulatein vitro glucose transport in adipocytes, cardiomyocytes and skeletal muscle, and to improvein vivo glucose utilization in rats. These effects were dependent on amine oxidation, since they were blocked by inhibitors of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO). We thus tested in this work whether a prolonged treatment with tyramine could improve glucose tolerance in streptozotocin-induced diabetic rats. First, tyramine content of standard rodent chow was determined by HPLC and daily tyramine intake of control rats was estimated to be around 26 μmol/kg body weight. Then, tyramine was administred during 3 weeks in streptozotocin-induced diabetic rats at 29 μmol/kg by daily i.p. injection alone or together with vanadate 0.02 μmol/kg. In another group of diabetic rats, tyramine was subcutaneously delivered at 116 μmol/kg/day by osmotic minipumps. All tyramine treatments resulted in a decrease of the hyperglycemic responses to an i.p. glucose load. Adipocytes isolated from either untreated or treated diabetic rats were sensitive to the stimulation of glucose uptake by tyramine. However, diabetic animals receiving tyramine for three weeks did not recover from their hyperglycemia, hypoinsulinemia and glucosuria. These results show that the improvement of glucose tolerance induced by prolonged tyramine administration occurs in an insulin-depleted model and probably results from peripheral insulin-like actions of the oxidation of MAO/SSAO substrates, such as the stimulation of glucose uptake into adipocytes.
Published: 2003

43. Hormone-sensitive lipase is a cholesterol esterase of the intestinal mucosa

Author: Jacques Grober, Maria Sörhede-Winzell, Philippe Besnard, Dominique Langin, Cecilia Holm, Isabelle Zaghini, Stéphanie Lucas, Juan Antonio Contreras, Aline Mairal, Laboratoire de Physiologie de la Nutrition, Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Cell and Molecular Biology [Uppsala], and Uppsala University
Subjects: Male, Diacylglycerol lipase, Transcription, Genetic, [SDV]Life Sciences [q-bio], Hormone-sensitive lipase, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Mice, Intestinal mucosa, Sterol esterase, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Lipase, Intestinal Mucosa, Lipoprotein, Molecular Biology, 030304 developmental biology, DNA Primers, 0303 health sciences, Lipoprotein lipase, biology, Base Sequence, Chemistry, 030302 biochemistry & molecular biology, digestive, oral, and skin physiology, food and beverages, Cell Biology, Sterol Esterase, Lipids, Small intestine, 3. Good health, Kinetics, Lipoprotein Lipase, medicine.anatomical_structure, biology.protein, Cholesteryl ester, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; The identity of the enzymes responsible for lipase and cholesterol esterase activities in the small intestinal mucosa is not known. Because hormone-sensitive lipase (HSL) catalyzes the hydrolysis of acylglycerols and cholesteryl esters, we sought to determine whether HSL could be involved. HSL mRNA and protein were detected in all segments of the small intestine by Northern and Western blot analyses, respectively. Immunocytochemistry experiments revealed that HSL was expressed in the differentiated enterocytes of the villi and was absent in the undifferentiated cells of the crypt. Diacylglycerol lipase and cholesterol esterase activities were found in the different segments. Analysis of gut from HSL-null mice showed that diacylglycerol lipase activity was unchanged in the duodenum and reduced in jejunum. Neutral cholesterol esterase activity was totally abolished in duodenum, jejunum, and ileum of HSL-null mice. Analysis of HSL mRNA structure showed two types of transcripts expressed in equal amounts with alternative 5′-ends transcribed from two exons. This work demonstrates that HSL is expressed in the mucosa of the small intestine. The results also reveal that the enzyme participates in acylglycerol hydrolysis in jejunal enterocytes and cholesteryl ester hydrolysis throughout the small intestine.
Published: 2002

44. In vitro and in vivo impairment of alpha2-adrenergic receptor-dependent antilipolysis by fatty acids in human adipose tissue

Author: Stephane Gesta, Jean Sébastien Saulnier-Blache, Vladimir Stich, Philippe Valet, François Crampes, Jindra Hejnova, Danièle Daviaud, Michel Berlan, Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Sport Medicine, Charles University [Prague] (CU), Laboratoire de Pharmacocinétique et de Toxicologie clinique [Toulouse], Université Toulouse III - Paul Sabatier (UT3), 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], Laboratoire des Adaptations de l'Organisme à l'Exercice Musculaire, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Saulnier-Blache, Jean Sébastien, 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 Pharmacocinétique et de Toxicologie [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: Glycerol, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Palmitates, Gene Expression, Adipose tissue, White adipose tissue, Biochemistry, MESH: Isoproterenol, MESH: Dose-Response Relationship, Drug, 0302 clinical medicine, Endocrinology, Idazoxan, Adipocytes, 0303 health sciences, Biopsy, Needle, Fatty Acids, General Medicine, Middle Aged, MESH: Idazoxan, MESH: Fatty Acids, Epinephrine, Adipose Tissue, MESH: Dietary Fats, Female, MESH: Adipose Tissue, medicine.drug, Adult, medicine.medical_specialty, Microdialysis, MESH: Biopsy, Needle, MESH: GTP-Binding Proteins, MESH: Gene Expression, Adrenergic receptor, MESH: Epinephrine, Lipolysis, 030209 endocrinology & metabolism, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Adrenergic Agents, Phentolamine, MESH: Glycerol, GTP-Binding Proteins, Receptors, Adrenergic, alpha-2, In vivo, Internal medicine, medicine, Humans, MESH: Lipolysis, Exercise, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Adipocytes, 030304 developmental biology, MESH: Humans, Dose-Response Relationship, Drug, Biochemistry (medical), Isoproterenol, MESH: Adult, MESH: Adrenergic Agents, Dietary Fats, MESH: Exercise, MESH: Female
Abstract: The aim of the present study was to study the influence of fatty acids on the adrenergic control of lipolysis both in vitro and in vivo. Human subcutaneous adipose tissue explants were cultured for 48 h in the presence of 100 microM bromopalmitate (BrPal), and lipolysis was measured in isolated adipocytes. In control conditions, beta-AR-dependent activation of lipolysis by epinephrine was almost undetectable, and could be fully restored by pharmacological blockade of alpha2-AR-dependent antilipolysis. After BrPal treatment, epinephrine became fully lipolytic and was no longer influenced by alpha2-AR-blockade. Radioligand binding analysis revealed that BrPal treatment led to a significant reduction in the coupling of alpha2-AR to G proteins. In parallel, a chronic and significant increase in plasma fatty acids resulting from a 4-day high-fat diet (HFD) was accompanied by an impairment of the amplifying effect of the alpha2-AR antagonist phentolamine on exercise-induced lipolysis (measured in the subcutaneous adipose tissue with the use of a microdialysis probe) normally observed after a low-fat diet. In conclusion, in vitro and in vivo studies showed that fatty acids impair alpha2-AR-dependent antilipolysis.
Published: 2001

45. Alpha2-adrenergic receptor-mediated release of lysophosphatidic acid by adipocytes. A paracrine signal for preadipocyte growth

Author: Philippe Valet, Michel Record, Max Lafontan, P. Barbe, Jean Sébastien Saulnier-Blache, Danièle Daviaud, Céline Pagès, Olivier Jeanneton, 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), Biologie de l'adipocyte, physiologie du tissu adipeux et obésités, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Louis Bugnard-Institut National de la Santé et de la Recherche Médicale (INSERM), Phospholipides membranaires, signalisation cellulaire et lipoprotéines, 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), and Saulnier-Blache, Jean Sébastien
Subjects: MESH: 3T3 Cells, Adipose tissue, Stimulation, White adipose tissue, chemistry.chemical_compound, Mice, Idazoxan, Adipocyte, Lysophosphatidic acid, Adipocytes, MESH: Receptors, MESH: Animals, Cells, Cultured, Cell Differentiation, MESH: Comparative Study, General Medicine, 3T3 Cells, MESH: Idazoxan, Actin Cytoskeleton, Brimonidine Tartrate, MESH: Cell Division, Female, lipids (amino acids, peptides, and proteins), Cell Division, Research Article, MESH: Cells, Cultured, Adult, MESH: Cell Differentiation, medicine.medical_specialty, Adrenergic receptor, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Actins, MESH: Lysophospholipids, Paracrine signalling, MESH: Quinoxalines, Receptors, Adrenergic, alpha-2, Internal medicine, Culture Techniques, Quinoxalines, Paracrine Communication, medicine, Animals, Humans, MESH: Paracrine Communication, MESH: Microfilaments, Autocrine signalling, MESH: Mice, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Adipocytes, MESH: Humans, MESH: Adult, Actins, Endocrinology, chemistry, MESH: Culture Techniques, Lysophospholipids, MESH: Female
Abstract: In the search for the existence of adrenergic regulation of the autocrine/paracrine function of the white adipose tissue, it was observed that conditioned media from isolated adipocytes or dialysates obtained by in situ microdialysis of human subcutaneous adipose tissue increased spreading and proliferation of 3T3F442A preadipocytes. These effects were amplified when an alpha2-adrenergic agonist was present during the obtention of conditioned media and microdialysates. This alpha2-adrenergic-dependent trophic activity was completely abolished by pretreatment of the conditioned media or microdialysates with the lysophospholipase, phospholipase B. Among the different lysophospholipids tested only lysophosphatidic acid (LPA) was able to induce spreading and proliferation of 3T3F442A preadipocytes. Moreover, previous chronic treatment of 3T3F442A preadipocytes with LPA which led to a specific desensitization of LPA responsiveness, abolished the alpha2-adrenergic-dependent trophic activities of the conditioned media and microdialysates. Finally, alpha2-adrenergic stimulation led to a rapid, sustained, and pertussis toxin-dependent release of [32P]LPA from [32P]-labeled adipocytes. Based upon these results it was proposed that in vitro and in situ stimulation of adipocyte alpha2-adrenergic receptors provokes the extracellular release of LPA leading, in turn, to regulation of preadipocyte growth.
Published: 1998

46. ApoB100-LDL Acts as a Metabolic Signal from Liver to Peripheral Fat Causing Inhibition of Lipolysis in Adipocytes

Author: Josefin Skogsberg, Hasanuzzaman Bhuiyan, Roland Nilsson, Anders Hamsten, Dominique Langin, Sigurd Vitols, Jesper Tegnér, Peter Arner, Johan Björkegren, Gaby Åström, Andrea Dicker, Erik Walum, Peteris Alberts, Mikael Rydén, Aline Mairal, The Computational Medicine Group, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department of medicine [Stockholm], Computational Biology Unit, Linköping University (LIU), Division of Clinical Pharmacology, 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), Biovitrum AB, Biovitrum, Atherosclerosis Research Unit, This study was supported by grants from the Swedish Research Council (P.Ar. and J.B.), the Swedish Diabetes Association (P.Ar.), the Swedish Heart-Lung Foundation (P.Ar., J.B., and A.H.), the Novo Nordic Foundation (P.Ar.) and the King Gustaf V and Queen Victoria Foundation (P.Ar., J.B.) and the European Commission, 6th Framework Program (contract LSHM-CT-2005-01873)., and Simon, Marie Francoise
Subjects: Male, MESH: Lipoproteins, LDL, Very low-density lipoprotein, Apolipoprotein B, Adipose tissue, White adipose tissue, Cell Biology/Cell Signaling, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH: Metabolic Syndrome X, Diabetes and Endocrinology/Endocrinology, Adipocytes, MESH: Animals, Metabolic Syndrome, MESH: Aged, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, MESH: Middle Aged, Multidisciplinary, biology, Chemistry, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Lipoproteins, LDL, MESH: Glucose, Diabetes and Endocrinology, Liver, MESH: Adipose Tissue, White, Apolipoprotein B-100, Medicine, lipids (amino acids, peptides, and proteins), Research Article, Adult, medicine.medical_specialty, Science, Adipose Tissue, White, Lipolysis, 030209 endocrinology & metabolism, 03 medical and health sciences, Lipid oxidation, 3T3-L1 Cells, Internal medicine, medicine, Animals, Humans, MESH: Lipolysis, MESH: Overweight, MESH: Mice, MESH: Adipocytes, Aged, 030304 developmental biology, MESH: Apolipoprotein B-100, MESH: Humans, Cholesterol, MESH: Adult, Overweight, MESH: 3T3-L1 Cells, MESH: Male, Glucose, Endocrinology, LDL receptor, biology.protein, MESH: Liver
Abstract: International audience; BACKGROUND: Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown. METHODS AND FINDINGS: We investigated the effects of apoB-containing lipoproteins on catecholamine-induced lipolysis in adipocytes from subcutaneous fat cells of obese but otherwise healthy men, fat pads from mice with plasma lipoproteins containing high or intermediate levels of apoB100 or no apoB100, primary cultured adipocytes, and 3T3-L1 cells. In subcutaneous fat cells, the rate of lipolysis was inversely related to plasma apoB levels. In human primary adipocytes, LDL inhibited lipolysis in a concentration-dependent fashion. In contrast, VLDL had no effect. Lipolysis was increased in fat pads from mice lacking plasma apoB100, reduced in apoB100-only mice, and intermediate in wild-type mice. Mice lacking apoB100 also had higher oxygen consumption and lipid oxidation. In 3T3-L1 cells, apoB100-containing lipoproteins inhibited lipolysis in a dose-dependent fashion, but lipoproteins containing apoB48 had no effect. ApoB100-LDL mediated inhibition of lipolysis was abolished in fat pads of mice deficient in the LDL receptor (Ldlr(-/-)Apob(100/100)). CONCLUSIONS: Our results show that the binding of apoB100-LDL to adipocytes via the LDL receptor inhibits intracellular noradrenaline-induced lipolysis in adipocytes. Thus, apoB100-LDL is a novel signaling molecule from the liver to peripheral fat deposits that may be an important link between atherogenic dyslipidemias and facets of the metabolic syndrome.
Published: 2008

47. Impaired fat-induced thermogenesis in obese subjects: The NUGENOB study

Author: Blaak, Ellen, Hul, Gabby, Verdich, Camilla, Stich, Vladimir, Martinez, J Alfredo, Petersen, Martin, Feskens, Edith, Patel, Kishor, Oppert, Jean-Michel, Barbe, Pierre, Toubro, Søren, Polák, Jan, Anderson, Ingalena, Astrup, Arne, Macdonald, Ian, Langin, Dominique, Sørensen, Thorkild, Saris, Wim, Consortium, Nugenob, Department of Human Biology (NUTRIM), Nutrition and Toxicology Research Institute Maastricht, Institute of Preventive Medicine, Copenhagen University Hospital, Department of Sports Medicine, Centre of Preventive Medicine, Third Faculty of Medicine Charles University, Department of Physiology and Nutrition, Universidad de Navarra [Pamplona] (UNAV), Institute of Human Nutrition, Royal Veterinary and Agricultural University = Kongelige Veterinær- og Landbohøjskole (KVL ), Division of Human Nutrition, Wageningen University and Research [Wageningen] (WUR), School of Biomedical Sciences, Queens Medical Centre, University of Nottingham Medical School, Service de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de l'Hôtel-Dieu, Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Humane Biologie, Epidemiologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: NUTRIM - R1 - Metabolic Syndrome, Simon, Marie Francoise, 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), 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, Nutrition and Disease, Hydrocortisone, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Fatty Acids, Nonesterified, adipose-tissue, Body Mass Index, 0302 clinical medicine, Endocrinology, Voeding en Ziekte, Adipocytes, Medicine, Insulin, MESH: Obesity, MESH: Thermogenesis, physical-activity, 2. Zero hunger, 0303 health sciences, MESH: Fatty Acids, Nonesterified, Nutrition and Dietetics, MESH: Middle Aged, MESH: Energy Metabolism, postprandial thermogenesis, Thermogenesis, Middle Aged, Postprandial Period, MESH: Hydrocortisone, MESH: Basal Metabolism, Postprandial, growth-hormone, MESH: Postprandial Period, Female, medicine.symptom, Adult, MESH: Triglycerides, medicine.medical_specialty, resting metabolic-rate, weight-gain, 030209 endocrinology & metabolism, MESH: Insulin, MESH: Body Mass Index, insulin-resistance, 03 medical and health sciences, Insulin resistance, Internal medicine, sympathetic neural activation, Humans, Resting energy expenditure, Obesity, Triglycerides, MESH: Adipocytes, 030304 developmental biology, VLAG, MESH: Humans, business.industry, food, energy-expenditure, MESH: Adult, medicine.disease, MESH: Male, Basal metabolic rate, Basal Metabolism, business, Energy Metabolism, Body mass index, Weight gain, MESH: Female
Abstract: International audience; OBJECTIVES: To study energy expenditure before and 3 hours after a high-fat load in a large cohort of obese subjects (n = 701) and a lean reference group (n = 113). RESEARCH METHODS AND PROCEDURES: Subjects from seven European countries underwent a 1-day clinical study with a liquid test meal challenge containing 95% fat (energy content was 50% of estimated resting energy expenditure). Fasting and 3-hour postprandial energy expenditures, as well as metabolites and hormones, were determined. RESULTS: Obese subjects had a reduced postprandial energy expenditure after the high-fat load, independent of body composition, age, sex, research center, and resting energy expenditure, whereas within the obese group, thermogenesis increased again with increasing BMI category. Additionally, insulin resistance, habitual physical activity, postprandial plasma triacylglycerols, and insulin were all independently positively related to the postprandial energy expenditure. Resting energy expenditure, adjusted for fat-free mass, increased with degree of obesity, a difference that disappeared after adjustment for fat mass. Furthermore, insulin resistance, fasting plasma free fatty acids, and cortisol were positively associated, whereas fasting plasma leptin and insulin-like growth factor-1 were negatively associated, with resting energy expenditure. DISCUSSION: The 3-hour fat-induced thermogenic response is reduced in obesity. It remains to be determined whether this blunted thermogenic response is a contributory factor or an adaptive response to the obese state.

48. Blood pressure disorders during Parkinson's disease: epidemiology, pathophysiology and management.

Author: Pathak A and Senard JM
Subjects: Antihypertensive Agents therapeutic use, Humans, Hypertension drug therapy, Hypertension epidemiology, Hypertension physiopathology, Hypotension, Orthostatic epidemiology, Hypotension, Orthostatic physiopathology, Hypertension etiology, Hypotension, Orthostatic etiology, Parkinson Disease physiopathology
Abstract: Blood pressure disorders are highly prevalent in the course of Parkinson's disease (PD). They relate to autonomic failure and are frequently associated with orthostatic hypotension, postprandial hypotension and supine hypertension. Supine hypertension, which may concern up to 50% of patients with PD and autonomic failure, is driven by residual sympathetic activity and changes in sensitivity of vascular adrenergic receptors. It can also be induced or worsened by antihypotensive drugs. Even if little data is available, a set of arguments suggests that supine hypertension sometimes requires treatment. This review will focus on recent data on the pathophysiology and the management of supine hypertension in the context of its association with orthostatic hypotension.
Published: 2006
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49. [Physiological and pathophysiological features of the control of lipolysis and lipid mobilization by natriuretic peptides].

Author: Moro C, Berlan M, and Lafontan M
Subjects: Adipose Tissue physiopathology, Cyclic GMP physiology, Exercise physiology, Humans, Models, Biological, Obesity physiopathology, Receptors, Atrial Natriuretic Factor physiology, Adipose Tissue physiology, Lipid Mobilization physiology, Lipolysis physiology, Natriuretic Peptides physiology
Abstract: We have demonstrated a potent and specific lipolytic effect of natriuretic peptides (NP) in human and primates' fat cells. The lipolytic effect of NP is mediated through intracellular production of cGMP and activation of the cGMP-dependent kinase 1alpha. Local infusion of atrial-NP (ANP), directly within the subcutaneous adipose tissue through a microdialysis catheter, increases lipolysis and stimulates blood flow through its vasodilating effect in lean healthy men. This effect is blunted in overweight men and can be recovered by endurance training. Intravenous infusion of physiological doses of ANP induces lipid mobilization. Higher concentrations of ANP that are encountered during heart failure also stimulate lipid oxidation. ANP activates lipolysis and free fatty acids release from adipose tissue during endurance exercise. This effect is paradoxically amplified when exercise is performed under beta-blockade treatment, because of an enhanced cardiac release of ANP. No gender differences in ANP-induced lipid mobilization during exercise have been found. Heart failure is associated with high circulating levels of NP that could participate to the progression toward cachexia. On contrary, a negative correlation between NP levels and body mass index is found in obese persons. The molecular basis of this inverse correlation is not yet demonstrated from a functional standpoint. Further studies are needed to clearly define the pathophysiological role of NP in obesity and heart failure.
Published: 2006
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50. [Fatty acid mobilization and their use in adipose tissue].

Author: Mazzucotelli A and Langin D
Subjects: Adipose Tissue physiopathology, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 physiopathology, Diabetes Mellitus, Type 2 prevention & control, Exercise, Humans, Lipolysis physiology, Models, Biological, Obesity physiopathology, Obesity prevention & control, Adipose Tissue physiology, Fatty Acids metabolism, Lipid Mobilization physiology
Abstract: An excess of fat mass excess predisposes to multiple complications such as type 2 diabetes, cardiovascular diseases or cancer. A dysregulation of lipid metabolism contributes to the development of obesity and the metabolic syndrome. Recent data on lipid mobilization in adipose tissue have revealed a complex pathway involving a human specific hormonal control of lipolysis via the natriuretic peptides and a new triglyceride lipase, ATGL. Activation of fatty acid reesterification and oxidation can lead to an increase in fatty acid utilization. Targeting these key steps of lipid metabolism (adipose tissue lipolysis and fatty acid oxidation) constitutes a potential strategy for the treatment of obesity and associated metabolic disorders.
Published: 2006
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