C. T. Montague, O. Rahilly, and S. , The perils of portliness: causes and consequences of visceral adiposity, Diabetes, vol.49, issue.6, pp.883-888, 2000.
DOI : 10.2337/diabetes.49.6.883

J. Cabau, O. F. Bertrand, and P. Poirier, Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk, Arterioscler. Thromb. Vasc. Biol, vol.28, pp.1039-1049, 2008.

Y. Deshaies, Mechanisms of the depot specificity of peroxisome proliferator-activated receptor gamma action on adipose tissue metabolism, Diabetes, vol.55, pp.2771-2778, 2006.

M. Lafontan and J. Girard, Impact of visceral adipose tissue on liver metabolism, Diabetes & Metabolism, vol.34, issue.4, pp.317-327, 2008.
DOI : 10.1016/j.diabet.2008.04.001

URL : https://hal.archives-ouvertes.fr/inserm-00420923

R. B. Goldberg, The new clinical trials with thiazolidinediones ??? DREAM, ADOPT, and CHICAGO: promises fulfilled?, Current Opinion in Lipidology, vol.18, issue.4, pp.435-442, 2007.
DOI : 10.1097/MOL.0b013e32821f604c

S. Heikkinen, J. Auwerx, and C. A. Argmann, PPAR?? in human and mouse physiology, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, vol.1771, issue.8, pp.999-1013, 2007.
DOI : 10.1016/j.bbalip.2007.03.006

L. Chao, B. Marcus-samuels, M. M. Mason, J. Moitra, C. Vinson et al., Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones, Journal of Clinical Investigation, vol.106, issue.10, pp.1221-1228, 2000.
DOI : 10.1172/JCI11245

W. He, Y. Barak, A. Hevener, P. Olson, D. Liao et al., Adipose-specific peroxisome proliferator-activated receptor ?? knockout causes insulin resistance in fat and liver but not in muscle, Proceedings of the National Academy of Sciences, vol.100, issue.26, pp.15712-15717, 2003.
DOI : 10.1073/pnas.2536828100

J. R. Jones, C. Barrick, K. A. Kim, J. Lindner, B. Blondeau et al., Deletion of PPAR?? in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance, Proceedings of the National Academy of Sciences, vol.102, issue.17, pp.6207-6212, 2005.
DOI : 10.1073/pnas.0306743102

P. Tontonoz, E. Hu, R. A. Graves, A. I. Budavari, and B. M. Spiegelman, mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer., Genes & Development, vol.8, issue.10, pp.1224-1234, 1994.
DOI : 10.1101/gad.8.10.1224

A. Chawla, E. J. Schwarz, D. D. Dimaculangan, and M. A. Lazar, Peroxisome proliferator-activated receptor (PPAR) (: Adipose-predominant expression and induction early in adipocyte differentiation, Endocrinology, vol.135, pp.798-800, 1994.

J. M. Lehmann, L. B. Moore, T. A. Smith-oliver, W. O. Wilkison, T. M. Willson et al., An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor ?? (PPAR??), Journal of Biological Chemistry, vol.270, issue.22, pp.12953-12956, 1995.
DOI : 10.1074/jbc.270.22.12953

S. L. Gray and A. J. Vidal-puig, Adipose Tissue Expandability in the Maintenance of Metabolic Homeostasis, Nutrition Reviews, vol.65, issue.6, pp.7-12, 2007.
DOI : 10.1301/nr.2007.jun.S7-S12

K. C. Choi, O. H. Ryu, K. W. Lee, H. Y. Kim, J. A. Seo et al., Effect of PPAR-alpha and -gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats, Biochem. Biophys. Res, 2005.

J. G. Yu, S. Javorschi, A. L. Hevener, Y. T. Kruszynska, R. A. Norman et al., The Effect of Thiazolidinediones on Plasma Adiponectin Levels in Normal, Obese, and Type 2 Diabetic Subjects, Diabetes, vol.51, issue.10, pp.2968-2974, 2002.
DOI : 10.2337/diabetes.51.10.2968

J. C. Sanchez, V. Converset, A. Nolan, G. Schmid, S. Wang et al., Effect of rosiglitazone on the differential expression of obesity and insulin resistance associated proteins inlep/lep mice, PROTEOMICS, vol.3, issue.8, pp.1500-1520, 2003.
DOI : 10.1002/pmic.200300484

Y. Zhu, C. Qi, C. Calandra, M. S. Rao, and J. K. Reddy, Cloning and identification of mouse steroid receptor coactivator-1 (mSRC-1), as a coactivator of peroxisome -24- proliferator-activated receptor gamma, Gene Expr, vol.6, pp.185-195, 1996.

L. Gelman, G. C. Zhou, L. Fajas, E. Raspe, J. C. Fruchart et al., p300 Interacts with the N- and C-terminal Part of PPAR??2 in a Ligand-independent and -dependent Manner, Respectively, Journal of Biological Chemistry, vol.274, issue.12, pp.7681-7688, 1999.
DOI : 10.1074/jbc.274.12.7681

C. X. Yuan, M. Ito, J. D. Fondell, Z. Y. Fu, and R. G. Roeder, The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion, Proc. Natl. Acad, 1998.
DOI : 10.1073/pnas.95.14.7939

P. Puigserver, Z. Wu, C. W. Park, R. Graves, M. Wright et al., A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis, Cell, vol.92, issue.6, pp.829-868, 1998.
DOI : 10.1016/S0092-8674(00)81410-5

C. Yu, K. Markan, K. A. Temple, D. Deplewski, M. J. Brady et al., The Nuclear Receptor Corepressors NCoR and SMRT Decrease Peroxisome Proliferator-activated Receptor ?? Transcriptional Activity and Repress 3T3-L1 Adipogenesis, Journal of Biological Chemistry, vol.280, issue.14, pp.13600-13605, 2005.
DOI : 10.1074/jbc.M409468200

H. P. Guan, T. Ishizuka, P. C. Chui, M. Lehrke, and M. A. Lazar, Corepressors selectively control the transcriptional activity of PPAR?? in adipocytes, Genes & Development, vol.19, issue.4, pp.453-461, 2005.
DOI : 10.1101/gad.1263305

R. R. Nofsinger, P. Li, S. H. Hong, J. W. Jonker, G. D. Barish et al., SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis, Proceedings of the National Academy of Sciences, vol.105, issue.50, pp.20021-20026, 2008.
DOI : 10.1073/pnas.0811012105

C. K. Glass and M. G. Rosenfeld, The coregulator exchange in transcriptional functions of nuclear receptors, Genes Dev, vol.14, pp.121-141, 2000.

R. Marfella, A. M. D-', F. C. Di, M. Siniscalchi, F. C. Sasso et al., The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes, Cardiovascular Diabetology, vol.6, issue.1, p.35, 2007.
DOI : 10.1186/1475-2840-6-35

S. Paul, Dysfunction of the ubiquitin-proteasome system in multiple disease conditions: therapeutic approaches, BioEssays, vol.104, issue.11-12, pp.1172-1184, 2008.
DOI : 10.1002/bies.20852

M. Boudjelal, Z. Q. Wang, J. J. Voorhees, and G. J. Fisher, Ubiquitin/proteasome pathway regulates levels of retinoic acid receptor gamma and retinoid X receptor alpha in human keratinocytes, Cancer Res, vol.60, pp.2247-2252, 2000.

F. Pettersson, N. Hanna, M. Lagodich, D. Dupere-richer, M. C. Couture et al., Rexinoids Modulate Steroid and Xenobiotic Receptor Activity by Increasing Its Protein Turnover in a Calpain-dependent Manner, Journal of Biological Chemistry, vol.283, issue.32, pp.21945-21952, 2008.
DOI : 10.1074/jbc.M710358200

M. G. Guenther, O. Barak, and M. A. Lazar, The SMRT and N-CoR Corepressors Are Activating Cofactors for Histone Deacetylase 3, Molecular and Cellular Biology, vol.21, issue.18, pp.6091-6101, 2001.
DOI : 10.1128/MCB.21.18.6091-6101.2001

K. Prufer and J. Barsony, Retinoid X Receptor Dominates the Nuclear Import and Export of the Unliganded Vitamin D Receptor, Molecular Endocrinology, vol.16, issue.8, pp.1738-1751, 2002.
DOI : 10.1210/me.2001-0345

A. Hershko, R. , and I. A. , Ubiquitin-aldehyde: a general inhibitor of ubiquitin-recycling processes., Proceedings of the National Academy of Sciences, vol.84, issue.7, pp.1829-1833, 1987.
DOI : 10.1073/pnas.84.7.1829

P. Trayhurn, B. Wang, and I. S. Wood, Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?, British Journal of Nutrition, vol.82, issue.02, pp.227-235, 2008.
DOI : 10.1210/en.2003-0580

Y. Liu, H. A. Lashuel, S. Choi, X. Xing, A. Case et al., Discovery of Inhibitors that Elucidate the Role of UCH-L1 Activity in the H1299 Lung Cancer Cell Line, Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line, pp.837-846, 2003.
DOI : 10.1016/j.chembiol.2003.08.010

D. J. Orlicky, J. Degregori, and J. Schaack, Construction of stable coxsackievirus and adenovirus receptor-expressing 3T3-L1 cells, J. Lipid Res, vol.42, pp.910-915, 2001.

J. Direnzo, M. Soderstrom, R. Kurokawa, M. H. Ogliastro, M. Ricote et al., Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors., Molecular and Cellular Biology, vol.17, issue.4, pp.2166-2176, 1997.
DOI : 10.1128/MCB.17.4.2166

A. K. El-jack, J. K. Hamm, P. F. Pilch, and S. R. Farmer, Reconstitution of insulinsensitive glucose transport in fibroblasts requires expression of both PPAR, 1999.

R. Setsuie and K. Wada, The functions of UCH-L1 and its relation to neurodegenerative diseases, Neurochemistry International, vol.51, issue.2-4, pp.105-111, 2007.
DOI : 10.1016/j.neuint.2007.05.007

H. Hayashi, Y. Kikuchi, and T. Nishikawa, Ubiquitin carboxyl-terminal hydrolase L1, a novel deubiquitinating enzyme in the vasculature, attenuates NF-kappaB activation, 2007.

G. C. Weir, Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets, Diabetes, vol.55, pp.1223-1231, 2006.

J. M. Huss, F. H. Levy, K. , and D. P. , Hypoxia Inhibits the Peroxisome Proliferator-activated Receptor ??/ Retinoid X Receptor Gene Regulatory Pathway in Cardiac Myocytes: A MECHANISM FOR O2-DEPENDENT MODULATION OF MITOCHONDRIAL FATTY ACID OXIDATION, Journal of Biological Chemistry, vol.276, issue.29, 2001.
DOI : 10.1074/jbc.M100277200

M. Ricote, S. Ngo, and J. Gemsch, Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes, Proc. Natl. Acad. Sci. U. S. A, vol.95, pp.2920-2925, 1998.

I. Zamir, J. Zhang, and M. A. Lazar, Stoichiometric and steric principles governing repression by nuclear hormone receptors., Genes & Development, vol.11, issue.7, pp.835-881, 1997.
DOI : 10.1101/gad.11.7.835

G. E. Muscat and T. A. Gustafson, Halofenate is a selective peroxisome proliferatoractivated receptor gamma modulator with antidiabetic activity, Diabetes, vol.55, pp.2523-2533, 2006.

P. Germain, J. Iyer, C. Zechel, and H. Gronemeyer, Co-regulator recruitment and the mechanism of retinoic acid receptor synergy, Nature, vol.415, issue.6868, pp.187-192, 2002.
DOI : 10.1038/415187a

H. Hauksdottir, B. Farboud, and M. L. Privalsky, Retinoic Acid Receptors ?? and ?? Do Not Repress, But Instead Activate Target Gene Transcription in Both the Absence and Presence of Hormone Ligand, Molecular Endocrinology, vol.17, issue.3, pp.373-385, 2003.
DOI : 10.1210/me.2002-0340

B. Farboud and M. L. Privalsky, Retinoic Acid Receptor-?? Is Stabilized in a Repressive State by Its C-Terminal, Isotype-Specific F Domain, Molecular Endocrinology, vol.18, issue.12, pp.2839-2853, 2004.
DOI : 10.1210/me.2004-0236

M. Schupp, M. Clemenz, R. Gineste, H. Witt, J. Janke et al., Molecular Characterization of New Selective Peroxisome Proliferator-Activated Receptor ?? Modulators With Angiotensin Receptor Blocking Activity, Diabetes, vol.54, issue.12, pp.3442-3452, 2005.
DOI : 10.2337/diabetes.54.12.3442

L. Gelman, J. N. Feige, and B. Desvergne, Molecular basis of selective PPAR?? modulation for the treatment of Type 2 diabetes, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, vol.1771, issue.8, pp.1094-1107, 2007.
DOI : 10.1016/j.bbalip.2007.03.004

B. Lefebvre, C. Brand, S. Flajollet, and P. Lefebvre, Down-Regulation of the Tumor Suppressor Gene Retinoic Acid Receptor ??2 through the Phosphoinositide 3-Kinase/Akt Signaling Pathway, Molecular Endocrinology, vol.20, issue.9, pp.2109-2121, 2006.
DOI : 10.1210/me.2005-0321

P. Sacchetti, H. Dwornik, P. Formstecher, C. Rachez, and P. Lefebvre, Requirements for Heterodimerization between the Orphan Nuclear Receptor Nurr1 and Retinoid X Receptors, Journal of Biological Chemistry, vol.277, issue.38, pp.35088-35096, 2002.
DOI : 10.1074/jbc.M205816200

F. J. Gonzalez, R. Gineste, and S. Helleboid, Regulation of human ApoA-I by gemfibrozil and fenofibrate through selective Peroxisome Proliferator-Activated Receptor" modulation, Arterioscler Thromb Vasc Biol, vol.25, pp.585-591, 2005.

C. Depoix, M. H. Delmotte, P. Formstecher, and P. Lefebvre, Control of retinoic acid receptor heterodimerization by ligand-induced structural transitions. a novel mechanism of action for retinoid antagonists, J. Biol. Chem, vol.276, pp.9452-9459, 2001.

B. M. Forman, The Antidiabetic Agent LG100754 Sensitizes Cells to Low Concentrations of Peroxisome Proliferator-activated Receptor ?? Ligands, Journal of Biological Chemistry, vol.277, issue.15, pp.12503-12506, 2002.
DOI : 10.1074/jbc.C200004200

A. M. Musti, M. Treier, and D. Bohmann, Reduced Ubiquitin-Dependent Degradation of c-Jun After Phosphorylation by MAP Kinases, Science, vol.275, issue.5298, pp.400-402, 1997.
DOI : 10.1126/science.275.5298.400

A. M. Musti, M. Treier, F. A. Peverali, and D. Bohmann, Differential Regulation of c-Jun and JunD by Ubiquitin-Dependent Protein Degradation, Biological Chemistry Hoppe-Seyler, vol.377, issue.10, pp.619-624, 1996.
DOI : 10.1515/bchm3.1996.377.10.619

S. Flajollet, B. Lefebvre, C. Rachez, and P. Lefebvre, Distinct Roles of the Steroid Receptor Coactivator 1 and of MED1 in Retinoid-induced Transcription and Cellular Differentiation, Journal of Biological Chemistry, vol.281, issue.29, pp.20338-20348, 2006.
DOI : 10.1074/jbc.M603023200

URL : https://hal.archives-ouvertes.fr/inserm-00079314

A. Mouchon, M. Delmotte, P. Formstecher, and P. Lefebvre, Allosteric Regulation of the Discriminative Responsiveness of Retinoic Acid Receptor to Natural and Synthetic Ligands by Retinoid X Receptor and DNA, Molecular and Cellular Biology, vol.19, issue.4, pp.3073-3085, 1999.
DOI : 10.1128/MCB.19.4.3073