help button home button Endocrine Society Endocrine Reviews
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
First published online on August 30, 2004
Endocrine Reviews, doi:10.1210/er.2003-0036
Endocrine Reviews, doi:10.1210/er.2003-0036
Endocrine Reviews 0 (2004): 200300361-
Copyright © 2004 by The Endocrine Society
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
25/6/899    most recent
Final Manuscript
Author Manuscript
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Knouff, C.
Right arrow Articles by Auwerx, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Knouff, C.
Right arrow Articles by Auwerx, J.

PPAR{gamma} calls for Activation in Moderation: Lessons from Genetics and Pharmacology

Chris Knouff and Johan Auwerx*

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS / INSERM / Université Louis Pasteur, 67404 Illkirch, France. Institut Clinique de la Souris, Génopole Strasbourg, 67404 Illkirch, France

* To whom correspondence should be addressed. E-mail: auwerx{at}igbmc.u-strasbg.fr.

The peroxisome proliferator-activated receptor gamma (PPAR{gamma}) is a prototypical member of the nuclear receptor superfamily and integrates the control of energy, lipid, and glucose homeostasis. PPAR{gamma} can bind a variety of small lipophillic compounds derived from metabolism and nutrition. These ligands in turn determine cofactor recruitment to PPAR{gamma}, regulating the transcription of genes in a variety of metabolic pathways. PPAR{gamma} is the main target of the thiazolidenedione class of insulin-sensitizing drugs, which are currently a mainstay of therapy for type 2 diabetes. However, this therapy has a number of side effects. Here, we review the clinical consequences of PPAR{gamma} polymorphisms in humans, as well as several studies in mice using general or tissue-specific knockout techniques. We also discuss the recent pharmacological literature describing a variety of new PPAR{gamma} partial agonists and antagonists, as well as pan-PPAR agonists. The results of these studies have added to the understanding of PPAR{gamma} function, allowing us to hypothesize a general mechanism of PPAR{gamma} action and speculate on future trends in the use of PPAR{gamma} as a target in the treatment of type II diabetes.
Key words: Nuclear Receptors • Obesity • Diabetes • Human Mutations • Mouse Models




This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
G. Bryzgalova, L. Lundholm, N. Portwood, J.-A. Gustafsson, A. Khan, S. Efendic, and K. Dahlman-Wright
Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice
Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E904 - E912.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
G. Orasanu, O. Ziouzenkova, P. R. Devchand, V. Nehra, O. Hamdy, E. S. Horton, and J. Plutzky
The Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Pioglitazone Represses Inflammation in a Peroxisome Proliferator-Activated Receptor-{alpha}-Dependent Manner In Vitro and In Vivo in Mice
J. Am. Coll. Cardiol., September 2, 2008; 52(10): 869 - 881.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
A. Montoudis, E. Seidman, F. Boudreau, J.-F. Beaulieu, D. Menard, M. Elchebly, G. Mailhot, A.-T. Sane, M. Lambert, E. Delvin, et al.
Intestinal fatty acid binding protein regulates mitochondrion {beta}-oxidation and cholesterol uptake
J. Lipid Res., May 1, 2008; 49(5): 961 - 972.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Li, Z. Wang, N. Furukawa, P. Escaron, J. Weiszmann, G. Lee, M. Lindstrom, J. Liu, X. Liu, H. Xu, et al.
T2384, a Novel Antidiabetic Agent with Unique Peroxisome Proliferator-activated Receptor {gamma} Binding Properties
J. Biol. Chem., April 4, 2008; 283(14): 9168 - 9176.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Bai, S. M. Houten, A. Huber, V. Schreiber, M. Watanabe, B. Kiss, G. de Murcia, J. Auwerx, and J. M.-d. Murcia
Peroxisome Proliferator-activated Receptor (PPAR)-2 Controls Adipocyte Differentiation and Adipose Tissue Function through the Regulation of the Activity of the Retinoid X Receptor/PPAR{gamma} Heterodimer
J. Biol. Chem., December 28, 2007; 282(52): 37738 - 37746.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. C. Carmona, K. Louche, B. Lefebvre, A. Pilon, N. Hennuyer, V. Audinot-Bouchez, C. Fievet, G. Torpier, P. Formstecher, P. Renard, et al.
S 26948: a New Specific Peroxisome Proliferator Activated Receptor {gamma} Modulator With Potent Antidiabetes and Antiatherogenic Effects
Diabetes, November 1, 2007; 56(11): 2797 - 2808.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. L. B. Ambrosio, S. M. G. Dias, I. Polikarpov, R. B. Zurier, S. H. Burstein, and R. C. Garratt
Ajulemic Acid, a Synthetic Nonpsychoactive Cannabinoid Acid, Bound to the Ligand Binding Domain of the Human Peroxisome Proliferator-activated Receptor {gamma}
J. Biol. Chem., June 22, 2007; 282(25): 18625 - 18633.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. Stienstra, S. Mandard, D. Patsouris, C. Maass, S. Kersten, and M. Muller
Peroxisome Proliferator-Activated Receptor {alpha} Protects against Obesity-Induced Hepatic Inflammation
Endocrinology, June 1, 2007; 148(6): 2753 - 2763.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. J. Kim, J.-Y. Hwang, H. J. Kim, W. S. Choi, J. H. Lee, H. J. Kim, K. C. Chang, T. Nishinaka, C. Yabe-Nishimura, and H. G. Seo
Expression of a Peroxisome Proliferator-Activated Receptor {gamma}1 Splice Variant that Was Identified in Human Lung Cancers Suppresses Cell Death Induced by Cisplatin and Oxidative Stress
Clin. Cancer Res., May 1, 2007; 13(9): 2577 - 2583.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
D. B. Savage, K. F. Petersen, and G. I. Shulman
Disordered Lipid Metabolism and the Pathogenesis of Insulin Resistance
Physiol Rev, April 1, 2007; 87(2): 507 - 520.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. C. Florez, K. A. Jablonski, M. W. Sun, N. Bayley, S. E. Kahn, H. Shamoon, R. F. Hamman, W. C. Knowler, D. M. Nathan, D. Altshuler, et al.
Effects of the Type 2 Diabetes-Associated PPARG P12A Polymorphism on Progression to Diabetes and Response to Troglitazone
J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1502 - 1509.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
C. Yang, S.-H. Jo, B. Csernus, E. Hyjek, Y. Liu, A. Chadburn, and Y. L. Wang
Activation of Peroxisome Proliferator-Activated Receptor {gamma} Contributes to the Survival of T Lymphoma Cells by Affecting Cellular Metabolism
Am. J. Pathol., February 1, 2007; 170(2): 722 - 732.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Scarsi, M. Podvinec, A. Roth, H. Hug, S. Kersten, H. Albrecht, T. Schwede, U. A. Meyer, and C. Rucker
Sulfonylureas and Glinides Exhibit Peroxisome Proliferator-Activated Receptor {gamma} Activity: A Combined Virtual Screening and Biological Assay Approach
Mol. Pharmacol., February 1, 2007; 71(2): 398 - 406.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
L. Michalik, J. Auwerx, J. P. Berger, V. K. Chatterjee, C. K. Glass, F. J. Gonzalez, P. A. Grimaldi, T. Kadowaki, M. A. Lazar, S. O'Rahilly, et al.
International Union of Pharmacology. LXI. Peroxisome Proliferator-Activated Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 726 - 741.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. L. Gray, E. Dalla Nora, E. C. Backlund, M. Manieri, S. Virtue, R. C. Noland, S. O'Rahilly, R. N. Cortright, S. Cinti, B. Cannon, et al.
Decreased Brown Adipocyte Recruitment and Thermogenic Capacity in Mice with Impaired Peroxisome Proliferator-Activated Receptor (P465L PPAR{gamma}) Function
Endocrinology, December 1, 2006; 147(12): 5708 - 5714.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J.-F. Louet, A. Coste, L. Amazit, M. Tannour-Louet, R.-C. Wu, S. Y. Tsai, M.-J. Tsai, J. Auwerx, and B. W. O'Malley
Oncogenic steroid receptor coactivator-3 is a key regulator of the white adipogenic program
PNAS, November 21, 2006; 103(47): 17868 - 17873.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S. L. Gray, E. D. Nora, J. Grosse, M. Manieri, T. Stoeger, G. Medina-Gomez, K. Burling, S. Wattler, A. Russ, G. S.H. Yeo, et al.
Leptin Deficiency Unmasks the Deleterious Effects of Impaired Peroxisome Proliferator-Activated Receptor {gamma} Function (P465L PPAR{gamma}) in Mice.
Diabetes, October 1, 2006; 55(10): 2669 - 2677.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
S Cheng, H Afif, J Martel-Pelletier, M Benderdour, J-P Pelletier, G Hilal, P Haraoui, J-P Raynauld, D Choquette, and H Fahmi
Association of polymorphisms in the peroxisome proliferator-activated receptor {gamma} gene and osteoarthritis of the knee.
Ann Rheum Dis, October 1, 2006; 65(10): 1394 - 1397.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
T. Allen, F. Zhang, S. A. Moodie, L. E. Clemens, A. Smith, F. Gregoire, A. Bell, G. E.O. Muscat, and T. A. Gustafson
Halofenate Is a Selective Peroxisome Proliferator-Activated Receptor {gamma} Modulator With Antidiabetic Activity
Diabetes, September 1, 2006; 55(9): 2523 - 2533.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. Barlic, Y. Zhang, J. F. Foley, and P. M. Murphy
Oxidized Lipid-Driven Chemokine Receptor Switch, CCR2 to CX3CR1, Mediates Adhesion of Human Macrophages to Coronary Artery Smooth Muscle Cells Through a Peroxisome Proliferator-Activated Receptor {gamma}-Dependent Pathway
Circulation, August 22, 2006; 114(8): 807 - 819.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Relic, V. Benoit, N. Franchimont, M.-J. Kaiser, J.-P. Hauzeur, P. Gillet, M.-P. Merville, V. Bours, and M. G. Malaise
Peroxisome Proliferator-activated Receptor-{gamma}1 Is Dephosphorylated and Degraded during BAY 11-7085-induced Synovial Fibroblast Apoptosis
J. Biol. Chem., August 11, 2006; 281(32): 22597 - 22604.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. Lopez-Soriano, C. Chiellini, M. Maffei, P. A. Grimaldi, and J. M. Argiles
Roles of Skeletal Muscle and Peroxisome Proliferator-Activated Receptors in the Development and Treatment of Obesity
Endocr. Rev., May 1, 2006; 27(3): 318 - 329.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters
The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR)
Toxicol. Sci., April 1, 2006; 90(2): 269 - 295.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Tsukahara, R. Tsukahara, S. Yasuda, N. Makarova, W. J. Valentine, P. Allison, H. Yuan, D. L. Baker, Z. Li, R. Bittman, et al.
Different Residues Mediate Recognition of 1-O-Oleyllysophosphatidic Acid and Rosiglitazone in the Ligand Binding Domain of Peroxisome Proliferator-activated Receptor {gamma}
J. Biol. Chem., February 10, 2006; 281(6): 3398 - 3407.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
M. M. Masternak, K. A. Al-Regaiey, M. M. Del Rosario Lim, V. Jimenez-Ortega, J. A. Panici, M. S. Bonkowski, J. J. Kopchick, and A. Bartke
Effects of Caloric Restriction and Growth Hormone Resistance on the Expression Level of Peroxisome Proliferator-Activated Receptors Superfamily in Liver of Normal and Long-Lived Growth Hormone Receptor/Binding Protein Knockout Mice
J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2005; 60(11): 1394 - 1398.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
M. M. Masternak, K. A. Al-Regaiey, M. M. Del Rosario Lim, M. S. Bonkowski, J. A. Panici, G. K. Przybylski, and A. Bartke
Caloric Restriction Results in Decreased Expression of Peroxisome Proliferator-Activated Receptor Superfamily in Muscle of Normal and Long-Lived Growth Hormone Receptor/Binding Protein Knockout Mice
J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2005; 60(10): 1238 - 1245.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
B. K. Chacko, R. T. Chandler, A. Mundhekar, N. Khoo, H. M. Pruitt, D. F. Kucik, D. A. Parks, C. G. Kevil, S. Barnes, and R. P. Patel
Revealing anti-inflammatory mechanisms of soy isoflavones by flow: modulation of leukocyte-endothelial cell interactions
Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H908 - H915.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Sabatino, A. Casamassimi, G. Peluso, M. V. Barone, D. Capaccio, C. Migliore, P. Bonelli, A. Pedicini, A. Febbraro, A. Ciccodicola, et al.
A Novel Peroxisome Proliferator-activated Receptor {gamma} Isoform with Dominant Negative Activity Generated by Alternative Splicing
J. Biol. Chem., July 15, 2005; 280(28): 26517 - 26525.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
E. Frohlich, F. Machicao, and R. Wahl
Action of thiazolidinediones on differentiation, proliferation and apoptosis of normal and transformed thyrocytes in culture
Endocr. Relat. Cancer, June 1, 2005; 12(2): 291 - 303.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2004 by The Endocrine Society