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Peroxisome proliferator-activated receptor γ, the ultimate liaison between fat and transcription

Published online by Cambridge University Press:  09 March 2007

Stéphane Rocchi  and
Johan Auwerx
Stéphane Rocchi
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire CNRS/INSERM/ULP, BP 163, F-67404 Illkirch cedex, C.U. de Strasbourg, France
Johan Auwerx*
Affiliation:
Institut de Génétique et de Biologie Moléculaire et Cellulaire CNRS/INSERM/ULP, BP 163, F-67404 Illkirch cedex, C.U. de Strasbourg, France
*
*Corresponding author: Johan Auwerx, tel +33 388653200, fax +33 388653203, email: [email protected]
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Abstract

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The peroxisome proliferator-activated receptor gamma (PPARγ) is nuclear receptor that controls the expression of a large number of genes involved in adipocyte differentiation, lipid storage and insulin sensitization. PPARγ is bound and activated by fatty acid derivatives and prostaglandin J2. In addition, thiazolidinediones, non-steroidal anti-inflammatory drugs are synthetic ligands and agonists of this receptor. This review addresses the role of PPARγ in obesity and diabetes.

Keywords

Adipose tissueGene expressionFatty acidsInsulin resistanceNuclear receptorsThiazolidinedionesType 2 diabetesTranscription
Type
Research Article
Information
British Journal of Nutrition , Volume 84 , Issue S2 , December 2000 , pp. S223 - S227
Copyright
Copyright © The Nutrition Society 2000

References

Auwerx, J & Staels, B (1998) Leptin. Lancet 351, 737–742.CrossRefGoogle ScholarPubMed
Beamer, BA, Yen, CJ, Andersen, RE, Muller, D, Elahi, D, Cheskin, LJ, Andres, R, Roth, J & Shuldiner, AR (1998) Association of the Pro12Ala variant in peroxisome proliferator-activated receptor gamma2 gene with obesity in two Caucasian populations. Diabetes 47, 1806–1808.CrossRefGoogle ScholarPubMed
Bouchard, C & Perusse, L (1993) Genetics of obesity. Annual Review of Nutrition 13, 337–354.CrossRefGoogle ScholarPubMed
Burant, CF, Sreenan, S, Hirano, K-I, Tai, T-AC, Lohmiller, J, Lukens, J, Davidson, NO, Ross, S & Graves, RA (1997) Troglitazone action is independent of adipose tissue. Journal of Clinical Investigation 100, 2900–2908.CrossRefGoogle ScholarPubMed
Cohen, B, Novick, D & Rubinstein, M (1996) Modulation of insulin activities by leptin. Science 274, 1185–1188.CrossRefGoogle ScholarPubMed
De Vos, P, Lefebvre, AM, Miller, SG, Guerre-Millo, M, Wong, K, Saladin, R, Hamann, L, Staels, B, Briggs, MR & Auwerx, J (1996) Thiazolidinediones repress ob gene expression via activation of PPARγ. Journal of Clinical Investigation 98, 1004–1009.CrossRefGoogle Scholar
Deeb, S, Fajas, L, Nemoto, M, Laakso, M, Fujimoto, W & Auwerx, J (1998) A Pro 12 Ala substitution in the human peroxisome proliferator-activated receptor gamma2 is associated with decreased receptor activity, improved insulin sensitivity, and lowered body mass index. Nature Genetics 20, 284–287.CrossRefGoogle Scholar
Desvergne, B & Wahli, W (1994) PPAR: a key nuclear factor in nutrient/gene interactions. In Inducible Gene Expression, vol. 1, pp. 142–176 [Bauerle, P, editors]. Boston: Birkhauser.Google Scholar
Ek, J, Urhammer, SA, Sorensen, TIA, Andersen, T, Auwerx, J & Pedersen, O (1999) Homozygosity of the Pro12Ala variant of the peroxisome proliferator activated receptor γ2 (PPARγ2): divergent modulating effects on body mass index in obese and lean men of Caucasian origin. Diabetologia 42, 892–895.CrossRefGoogle Scholar
Fajas, L, Auboeuf, D, Raspe, E, Schoonjans, K, Lefebvre, AM, Saladin, R, Najib, J, Laville, M, Fruchart, JC, Deeb, S, Vidal-Puig, A, Flier, J, Briggs, MR, Staels, B, Vidal, H & Auwerx, J (1997) Organization, promoter analysis and expression of the human PPARγ gene. Journal of Biological Chemistry 272, 18779–18789.CrossRefGoogle ScholarPubMed
Fajas, L, Fruchart, JC & Auwerx, J (1998) Transcriptional control of adipogenesis. Current Opinions in Cell Biology 10, 165–173.CrossRefGoogle ScholarPubMed
Fajas, L, Schoonjans, K, Gelman, L, Kim, JB, Najib, J, Martin, G, Fruchart, JC, Briggs, M, Spiegelman, BM & Auwerx, J (1999) Regulation of PPARγ expression by ADD-1/SREBP-1: implications for adipocyte differentiation and metabolism. Molecular Cellular Biology 19, 5495–5503.CrossRefGoogle ScholarPubMed
Gelman, L, Fruchart, J-C & Auwerx, J (1999) An update on the mechanisms of action of the peroxisome proliferator-activated receptors (PPARs) and their roles in inflammation and cancer. Cellular and Molecular Life Sciences 55, 932–943.CrossRefGoogle ScholarPubMed
Hofmann, C, Lorenz, K, Braithwaite, SS, Colca, JR, Palazuk, BJ, Hotamisligil, GS & Spiegelman, BM (1994) Altered gene expression for tumor necrosis factor-α and its receptor during drug and dietary modulation of insulin resistance. Endocrinology 134, 264–270.CrossRefGoogle ScholarPubMed
Hotamisligil, GS, Arner, P, Caro, JF, Atkinson, RL & Spiegelman, BM (1995) Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. Journal of Clinical Investigation 95, 2409–2415.CrossRefGoogle ScholarPubMed
Hotamisligil, GS, Peraldi, P, Budavari, A, Ellis, R, White, MF & Spiegelman, BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity induced insulin resistance. Science 271, 665–668.CrossRefGoogle ScholarPubMed
Hui, TY, Frohnert, BI, Smith, AJ, Schaffer, JE & Bernlohr, DA (1998) Characterization of the murine fatty acid transport protein gene and its insulin response sequence. Journal of Biological Chemistry 273, 27420–27429.CrossRefGoogle ScholarPubMed
Kim, JB & Spiegelman, BM (1996) ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes and Development 10, 1096–1107.CrossRefGoogle ScholarPubMed
Liu, YL, Emilson, V & Cawthorne, MA (1997) Leptin inhibits glycogen synthesis in isolated soleus muscle of obese (ob/ob) mice. FEBS Letters 411, 351–355.CrossRefGoogle ScholarPubMed
Lopez, JM, Bennett, MK, Sanchez, HB, Rosenfeld, JM & Osborne, TF (1996) Sterol regulation of acetyl coenzyme A carboxylase: a mechanism for coordinate control of cellular lipid. Proceedings of the National Academy of Sciences USA 93, 1049–1053.CrossRefGoogle ScholarPubMed
Martin, G, Schoonjans, K, Lefebvre, A, Staels, B & Auwerx, J (1997) Coordinate regulation of the expression of the fatty acid transport protein (FATP) and acyl CoA synthetase genes by PPARα and PPARγ activators. Journal of Biological Chemistry 272, 28210–28217.CrossRefGoogle ScholarPubMed
Martin, G, Schoonjans, K, Staels, B & Auwerx, J (1998) PPARγ activators improve glucose homeostasis by stimulating fatty acid uptake in the adipocytes. Atherosclerosis 137, 75–80.CrossRefGoogle ScholarPubMed
Miller, SG, De Vos, P, Guerre-Millo, M, Wong, K, Hermann, T, Staels, B, Briggs, MR & Auwerx, J (1996) The adipocyte specific transcription factor. C/EBPα modulates human ob gene expression. Proceedings of the National Academy of Sciences USA 93, 5507–5511.CrossRefGoogle ScholarPubMed
Moitra, J, Mason, MM, Olive, M, Krylov, D, Gavrilova, O, Marcus-Samuels, B, Feigenbaum, L, Lee, E, Aoyama, T, Eckhaus, M, Reitman, ML & Vinson, C (1998) Life without fat: a transgenic mouse. Genes and Development 12, 3168–3181.CrossRefGoogle ScholarPubMed
Moller, DE & Flier, JS (1991) Insulin resistance: mechanisms, syndromes, and implications. New England Journal of Medicine 325, 938–948.Google ScholarPubMed
Mori, Y, Kim-Motoyama, H, Katakura, T, Yasuda, K, Kadowaki, H, Beamer, BB, Shuldiner, AR, Akanuma, Y, Yazaki, Y & Kadowaki, T (1998) Effect of the Pro12Ala variant of the human peroxisome proliferator activated receptor γ2 gene on adiposity, fat distribution, and insulin sensitivity in Japanese men. Biochemical and Biophysical Research Communications 251, 195–198.CrossRefGoogle Scholar
Peraldi, P, Xu, M & Spiegelman, BM (1997) Thiazolidinediones block tumor necrosis factor-a-induced inhibition of insulin signaling. Journal of Clinical Investigation 100, 1863–1869.CrossRefGoogle Scholar
Randle, PJ, Garland, PB, Hales, CN & Newsholme, EA (1961) The glucose-fatty acid cycle: its role in insulin sensitivity and metabolic disturbances of diabetes mellitus. Lancet I, 785–789.Google Scholar
Ribon, V, Johnson, JH, Camp, HS & Saltiel, AR (1998) Thiazolidinediones and insulin resistance: peroxisome proliferator-activated receptor γ activation stimulates expression of the CAP gene. Proceedings of the National Academy of Sciences USA 95, 14751–14756.CrossRefGoogle ScholarPubMed
Ristow, M, Muller-Wieland, D, Pfeiffer, A, Krone, W & Kahn, CR (1998) Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. New England Journal of Medicine 339, 953–959.CrossRefGoogle Scholar
Saladin, R, Fajas, L, Dana, S, Halvorsen, YD, Auwerx, J & Briggs, M (1999) Differential regulation of peroxisome proliferator activated receptor γ1 (PPARγ1) and PPARγ2 mRNA expession in early stages of adipogenesis. Cell Growth Differentiation 10, 43–48.Google Scholar
Schoonjans, K, Marin, G, Staels, B & Auwerx, J (1997) Peroxisome proliferator-activated receptors, orphans with ligands and functions. Current Opinion in Lipidology 8, 159–165.CrossRefGoogle ScholarPubMed
Schoonjans, K, Peinado-Onsurbe, J, Lefebvre, AM, Heyman, R, Briggs, M, Deeb, S, Staels, B & Auwerx, J (1996) PPARα and PPARγ activators direct a tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 15, 5336–5348.CrossRefGoogle Scholar
Schoonjans, K, Staels, B, Grimaldi, P & Auwerx, J (1993) Acyl-CoA synthetase mRNA expression is controlled by fibric-acid derivatives, feeding and liver proliferation. European Journal of Biochemistry 216, 615–622.CrossRefGoogle ScholarPubMed
Schoonjans, K, Watanabe, M, Suzuki, H, Mahfoudi, A, Krey, G, Wahli, W, Grimaldi, P, Staels, B, Yamamoto, T & Auwerx, J (1995) Induction of the Acyl-Coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter. Journal of Biological Chemistry 270, 19269–19276.CrossRefGoogle ScholarPubMed
Shao, D & Lazar, MA (1997) Peroxisome proliferator activated receptor γ, CCAAT/enhancer binding protein a, and cell cycle status regulate the commitment to adipocyte differentiation. Journal of Biological Chemistry 272, 21473–21478.CrossRefGoogle ScholarPubMed
Shao, D, Rangwala, SM, Bailey, ST, Krakow, SL, Reginato, MJ & Lazar, MA (1998) Interdomain communication regulating ligand binding by PPAR gamma. Nature 396, 377–380.CrossRefGoogle ScholarPubMed
Shimano, H, Horton, JD, Hammer, RE, Shimomura, I, Brown, MS & Goldstein, JL (1996) Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. Journal of Clinical Investigation 98, 1575–1584.CrossRefGoogle ScholarPubMed
Shimomura, I, Hammer, RE, Richardson, JA, Ikemoto, S, Bashmakov, YJLG & Brown, MS (1998) Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: a model for congenital generalized lipodystrophy. Genes and Development 12, 3182–3194.CrossRefGoogle Scholar
Tontonoz, P, Hu, E, Devine, J, Beale, EG & Spiegelman, BM (1995) PPARγ2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Molecular Cellular Biology 15, 351–357.CrossRefGoogle ScholarPubMed
Tontonoz, P, Hu, E, Graves, RA, Budavari, AI & Spiegelman, BM (1994 a) mPPARγ2: tissue-specific regulator of an adipocyte enhancer. Genes and Development 8, 1224–1234.CrossRefGoogle ScholarPubMed
Tontonoz, P, Hu, E & Spiegelman, BM (1994 b) Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell 79, 1147–1156.CrossRefGoogle ScholarPubMed
Tontonoz, P, Nagy, L, Alvarez, JG, Thomazy, VA & Evans, RM (1998) PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 93, 241–252.CrossRefGoogle ScholarPubMed
Torti, FM, Dieckman, B, Beutler, B, Cerami, A & Ringold, GM (1985) A macrophage factor inhibits adipocyte gene expression; an in vitro model for cachexia. Science 229, 867–869.CrossRefGoogle Scholar
Vigouroux, C, Fajas, L, Khallouf, E, Meier, M, Gyapay, G, Auwerx, J, Weissenbach, J, Capeau, J & Magre, J (1998) Human peroxisome proliferator-activated receptor gamma 2: genetic mapping, identification of a variant in the coding sequence, and exclusion as the gene responsable for lipoatrophic diabetes. Diabetes 47, 490–492.CrossRefGoogle Scholar
Werman, A, Hollenberg, A, Solanes, G, Bjorbaek, C, Vidal-Puig, A & Flier, JS (1997) Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor γ (PPARγ). Journal of Biological Chemistry 272, 20230–20235.CrossRefGoogle Scholar
Whitaker, RC, Wright, JA, Pepe, MS, Seidel, KD & Dietz, WH (1997) Predicting obesity in young adulthood from childhood and parental obesity. New England Journal of Medicine 337, 869–873.CrossRefGoogle ScholarPubMed
Williams, PM, Chang, DJ, Danesch, U, Ringold, GM & Heller, RA (1992) CCAAT/enhancer binding protein expression is rapidly extinguished in TA1 adipocyte cells treated with tumor necrosis factor. Molecular Endocrinology 6, 1135–1141.Google Scholar
Wu, Z, Bucher, NLR & Farmer, SR (1996) Induction of peroxisome proliferator-activated receptor γ during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPβ, C/EBPδ, and glucocorticoids. Molecular Cellular Biology 16, 4128–4136.CrossRefGoogle Scholar
Wu, Z, Xie, Y, Morrison, RF, Bucher, NLR & Farmer, SR (1998) PPARγ induces the insulin-dependent glucose transporter GLUT4 in absence of C/EBPα during the conversion of 3T3 fibroblast into adipocytes. Journal of Clinical Investigation 101, 22–32.CrossRefGoogle ScholarPubMed
Yen, CJ, Beamer, BA, Negri, C, Silver, K, Brown, KA, Yarnall, DP, Burns, DK, Roth, J & Shuldiner, AR (1997) Molecular scanning of the human peroxisome proliferator activated receptor gamma gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochemical and Biophysical Research Communications 241, 270–274.CrossRefGoogle ScholarPubMed