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Endocrine Reviews 20 (5): 649
Copyright © 1999 by The Endocrine Society

Peroxisome Proliferator-Activated Receptors: Nuclear Control of Metabolism1

Béatrice Desvergne and Walter Wahli

Institute of Animal Biology, University of Lausanne, CH-1015 Lausanne, Switzerland

I. Introduction
II. Molecular Aspects
A. PPAR isotypes: identity, genomic organization and chromosomal localization
B. DNA binding properties
C. PPAR ligand-binding properties
D. Alternative pathways for PPAR activation
E. PPAR-mediated transactivation properties
III. Physiological Aspects
A. Differential expression of PPAR mRNAs
B. PPAR target genes and functions in fatty acid metabolism
C. PPARs and control of inflammatory responses
D. PPARs and atherosclerosis
E. PPARs and the development of the fetal epidermal permeability barrier
F. PPARs, carcinogenesis, and control of the cell cycle
IV. Conclusions




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G. D'Agostino, G. La Rana, R. Russo, O. Sasso, A. Iacono, E. Esposito, G. M. Raso, S. Cuzzocrea, J. Lo Verme, D. Piomelli, et al.
Acute Intracerebroventricular Administration of Palmitoylethanolamide, an Endogenous Peroxisome Proliferator-Activated Receptor-{alpha} Agonist, Modulates Carrageenan-Induced Paw Edema in Mice
J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 1137 - 1143.
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 J. Biol. Chem.Home page
J. Tordjman, S. Leroyer, G. Chauvet, J. Quette, C. Chauvet, C. Tomkiewicz, C. Chapron, R. Barouki, C. Forest, M. Aggerbeck, et al.
Cytosolic Aspartate Aminotransferase, a New Partner in Adipocyte Glyceroneogenesis and an Atypical Target of Thiazolidinedione
J. Biol. Chem., August 10, 2007; 282(32): 23591 - 23602.
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 Toxicol SciHome page
B. D. Abbott, C. J. Wolf, J. E. Schmid, K. P. Das, R. D. Zehr, L. Helfant, S. Nakayama, A. B. Lindstrom, M. J. Strynar, and C. Lau
Perfluorooctanoic Acid Induced Developmental Toxicity in the Mouse is Dependent on Expression of Peroxisome Proliferator Activated Receptor-alpha
Toxicol. Sci., August 1, 2007; 98(2): 571 - 581.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
B. E.J. Teunissen, P. J.H. Smeets, P. H.M. Willemsen, L. J. De Windt, G. J. Van der Vusse, and M. Van Bilsen
Activation of PPAR{delta} inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts
Cardiovasc Res, August 1, 2007; 75(3): 519 - 529.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
P. D. Gluckman, K. A. Lillycrop, M. H. Vickers, A. B. Pleasants, E. S. Phillips, A. S. Beedle, G. C. Burdge, and M. A. Hanson
Metabolic plasticity during mammalian development is directionally dependent on early nutritional status
PNAS, July 31, 2007; 104(31): 12796 - 12800.
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 J. Biol. Chem.Home page
P. Degrace, L. Demizieux, Z.-y. Du, J. Gresti, L. Caverot, L. Djaouti, T. Jourdan, B. Moindrot, J.-C. Guilland, J.-F. Hocquette, et al.
Regulation of Lipid Flux between Liver and Adipose Tissue during Transient Hepatic Steatosis in Carnitine-depleted Rats
J. Biol. Chem., July 20, 2007; 282(29): 20816 - 20826.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
M. Takeda, F. Otsuka, H. Otani, K. Inagaki, T. Miyoshi, J. Suzuki, Y. Mimura, T. Ogura, and H. Makino
Effects of peroxisome proliferator-activated receptor activation on gonadotropin transcription and cell mitosis induced by bone morphogenetic proteins in mouse gonadotrope L{beta}T2 cells
J. Endocrinol., July 1, 2007; 194(1): 87 - 99.
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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Luci, B. Giemsa, H. Kluge, and K. Eder
Clofibrate causes an upregulation of PPAR-{alpha} target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R70 - R77.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
A. Guellich, T. Damy, Y. Lecarpentier, M. Conti, V. Claes, J.-L. Samuel, J. Quillard, J.-L. Hebert, T. Pineau, and C. Coirault
Role of oxidative stress in cardiac dysfunction of PPAR{alpha}-/- mice
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H93 - H102.
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 J. Biol. Chem.Home page
W.-L. Chou, L.-M. Chuang, C.-C. Chou, A. H.-J. Wang, J. A. Lawson, G. A. FitzGerald, and Z.-F. Chang
Identification of a Novel Prostaglandin Reductase Reveals the Involvement of Prostaglandin E2 Catabolism in Regulation of Peroxisome Proliferator-activated Receptor {gamma} Activation
J. Biol. Chem., June 22, 2007; 282(25): 18162 - 18172.
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 J. Biol. Chem.Home page
N. Viswakarma, S. Yu, S. Naik, P. Kashireddy, K. Matsumoto, J. Sarkar, S. Surapureddi, Y. Jia, M. S. Rao, and J. K. Reddy
Transcriptional Regulation of Cidea, Mitochondrial Cell Death-inducing DNA Fragmentation Factor {alpha}-Like Effector A, in Mouse Liver by Peroxisome Proliferator-activated Receptor {alpha} and {gamma}
J. Biol. Chem., June 22, 2007; 282(25): 18613 - 18624.
[Abstract] [Full Text] [PDF]

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 Epidemiol RevHome page
W. Yang, T. Kelly, and J. He
Genetic Epidemiology of Obesity
Epidemiol. Rev., June 12, 2007; (2007) mxm004v1.
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 J. Biol. Chem.Home page
G. Pochetti, C. Godio, N. Mitro, D. Caruso, A. Galmozzi, S. Scurati, F. Loiodice, G. Fracchiolla, P. Tortorella, A. Laghezza, et al.
Insights into the Mechanism of Partial Agonism: CRYSTAL STRUCTURES OF THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR {gamma} LIGAND-BINDING DOMAIN IN THE COMPLEX WITH TWO ENANTIOMERIC LIGANDS
J. Biol. Chem., June 8, 2007; 282(23): 17314 - 17324.
[Abstract] [Full Text] [PDF]

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 Toxicol PatholHome page
P. D. Cornwell and R. G. Ulrich
Investigating the Mechanistic Basis for Hepatic Toxicity Induced by an Experimental Chemokine Receptor 5 (CCR5) Antagonist Using a Compendium of Gene Expression Profiles
Toxicol Pathol, June 1, 2007; 35(4): 576 - 588.
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 Poult. Sci.Home page
B. Konig, H. Kluge, K. Haase, C. Brandsch, G. I. Stangl, and K. Eder
Effects of Clofibrate Treatment in Laying Hens
Poult. Sci., June 1, 2007; 86(6): 1187 - 1195.
[Abstract] [Full Text] [PDF]

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 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.
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 J. Nutr.Home page
A. Diez, D. Menoyo, S. Perez-Benavente, J. A. Calduch-Giner, S. Vega-Rubin de Celis, A. Obach, L. Favre-Krey, E. Boukouvala, M. J. Leaver, D. R. Tocher, et al.
Conjugated Linoleic Acid Affects Lipid Composition, Metabolism, and Gene Expression in Gilthead Sea Bream (Sparus aurata L)
J. Nutr., June 1, 2007; 137(6): 1363 - 1369.
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 J. Immunol.Home page
F. Zapata-Gonzalez, F. Rueda, J. Petriz, P. Domingo, F. Villarroya, A. de Madariaga, and J. C. Domingo
9-cis-Retinoic Acid (9cRA), a Retinoid X Receptor (RXR) Ligand, Exerts Immunosuppressive Effects on Dendritic Cells by RXR-Dependent Activation: Inhibition of Peroxisome Proliferator-Activated Receptor {gamma} Blocks Some of the 9cRA Activities, and Precludes Them to Mature Phenotype Development
J. Immunol., May 15, 2007; 178(10): 6130 - 6139.
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 Molecular Cancer TherapeuticsHome page
S. Chintharlapalli, S. Papineni, I. Jutooru, A. McAlees, and S. Safe
Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator-activated receptor {gamma} agonists in colon cancer cells
Mol. Cancer Ther., May 1, 2007; 6(5): 1588 - 1598.
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 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]

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 DiabetesHome page
E. Arikawa, R. C.W. Ma, K. Isshiki, I. Luptak, Z. He, Y. Yasuda, Y. Maeno, M. E. Patti, G. C. Weir, R. A. Harris, et al.
Effects of Insulin Replacements, Inhibitors of Angiotensin, and PKC{beta}'s Actions to Normalize Cardiac Gene Expression and Fuel Metabolism in Diabetic Rats
Diabetes, May 1, 2007; 56(5): 1410 - 1420.
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 Circ. Res.Home page
J. Yang, N. Sambandam, X. Han, R. W. Gross, M. Courtois, A. Kovacs, M. Febbraio, B. N. Finck, and D. P. Kelly
CD36 Deficiency Rescues Lipotoxic Cardiomyopathy
Circ. Res., April 27, 2007; 100(8): 1208 - 1217.
[Abstract] [Full Text] [PDF]

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 JCOHome page
R. Govindarajan, L. Ratnasinghe, D. L. Simmons, E. R. Siegel, M. V. Midathada, L. Kim, P. J. Kim, R. J. Owens, and N. P. Lang
Thiazolidinediones and the Risk of Lung, Prostate, and Colon Cancer in Patients With Diabetes
J. Clin. Oncol., April 20, 2007; 25(12): 1476 - 1481.
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 J. Biol. Chem.Home page
D. Genini and C. V. Catapano
Block of Nuclear Receptor Ubiquitination: A MECHANISM OF LIGAND-DEPENDENT CONTROL OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR {delta} ACTIVITY
J. Biol. Chem., April 20, 2007; 282(16): 11776 - 11785.
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 J. Lipid Res.Home page
A. Gatica, M. C. Aguilera, D. Contador, G. Loyola, C. O. Pinto, L. Amigo, J. E. Tichauer, S. Zanlungo, and M. Bronfman
P450 CYP2C epoxygenase and CYP4A {omega}-hydroxylase mediate ciprofibrate-induced PPAR{alpha}-dependent peroxisomal proliferation
J. Lipid Res., April 1, 2007; 48(4): 924 - 934.
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 J. Biol. Chem.Home page
L. Michalik, V. Zoete, G. Krey, A. Grosdidier, L. Gelman, P. Chodanowski, J. N. Feige, B. Desvergne, W. Wahli, and O. Michielin
Combined Simulation and Mutagenesis Analyses Reveal the Involvement of Key Residues for Peroxisome Proliferator-activated Receptor{alpha} Helix 12 Dynamic Behavior
J. Biol. Chem., March 30, 2007; 282(13): 9666 - 9677.
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 J Mol EndocrinolHome page
M. J Leaver, M T. Ezaz, S. Fontagne, D. R Tocher, E. Boukouvala, and G. Krey
Multiple peroxisome proliferator-activated receptor {beta} subtypes from Atlantic salmon (Salmo salar)
J. Mol. Endocrinol., March 1, 2007; 38(3): 391 - 400.
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 Diabetes and Vascular Disease ResearchHome page
C. J Bailey
Treating insulin resistance: future prospects
Diabetes and Vascular Disease Research, March 1, 2007; 4(1): 20 - 31.
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 J EndocrinolHome page
K. Han, H. Song, I. Moon, R. Augustin, K. Moley, M. Rogers, and H. Lim
Utilization of DR1 as true RARE in regulating the Ssm, a novel retinoic acid-target gene in the mouse testis
J. Endocrinol., March 1, 2007; 192(3): 539 - 551.
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 Drug Metab. Dispos.Home page
K. Senekeo-Effenberger, S. Chen, E. Brace-Sinnokrak, J. A. Bonzo, M.-F. Yueh, U. Argikar, J. Kaeding, J. Trottier, R. P. Remmel, J. K. Ritter, et al.
Expression of the Human UGT1 Locus in Transgenic Mice by 4-Chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic Acid (WY-14643) and Implications on Drug Metabolism through Peroxisome Proliferator-Activated Receptor {alpha} Activation
Drug Metab. Dispos., March 1, 2007; 35(3): 419 - 427.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
B. P. Atshaves, A. L. McIntosh, D. Landrock, H. R. Payne, J. T. Mackie, N. Maeda, J. Ball, F. Schroeder, and A. B. Kier
Effect of SCP-x gene ablation on branched-chain fatty acid metabolism
Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G939 - G951.
[Abstract] [Full Text] [PDF]

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 JEMHome page
S. E. Dunn, S. S. Ousman, R. A. Sobel, L. Zuniga, S. E. Baranzini, S. Youssef, A. Crowell, J. Loh, J. Oksenberg, and L. Steinman
Peroxisome proliferator-activated receptor (PPAR){alpha} expression in T cells mediates gender differences in development of T cell-mediated autoimmunity
J. Exp. Med., February 19, 2007; 204(2): 321 - 330.
[Abstract] [Full Text] [PDF]

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 Eur J EndocrinolHome page
A Majuri, M Santaniemi, K Rautio, A Kunnari, J Vartiainen, A Ruokonen, Y A Kesaniemi, J S Tapanainen, O Ukkola, and L Morin-Papunen
Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with PCOS: a randomized placebo-controlled study
Eur. J. Endocrinol., February 1, 2007; 156(2): 263 - 269.
[Abstract] [Full Text] [PDF]

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 J. Exp. Biol.Home page
D. Maillet and J.-M. Weber
Relationship between n-3 PUFA content and energy metabolism in the flight muscles of a migrating shorebird: evidence for natural doping
J. Exp. Biol., February 1, 2007; 210(3): 413 - 420.
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 J. Appl. Physiol.Home page
D. Freyssenet
Energy sensing and regulation of gene expression in skeletal muscle
J Appl Physiol, February 1, 2007; 102(2): 529 - 540.
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