Peroxisome proliferator-activated receptor gamma

Available structures
PDBOrtholog search: PDBe RCSB
Aliases PPARG, CIMT1, GLM1, NR1C3, PPARG1, PPARG2, PPARgamma, peroxisome proliferator activated receptor gamma
External IDs MGI: 97747 HomoloGene: 7899 GeneCards: PPARG
Genetically Related Diseases
type 2 diabetes mellitus[1]
Targeted by Drug
rosiglitazone, ciglitazone, linoleic acid, mesalamine, netoglitazone, pioglitazone, Troglitazone, farglitazar, indomethacin, bexarotene, bardoxolone methyl, diclofenac, resveratrol[2]
RNA expression pattern
More reference expression data
Species Human Mouse









RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 3: 12.29 – 12.43 Mb Chr 6: 115.36 – 115.49 Mb
PubMed search [3] [4]
View/Edit HumanView/Edit Mouse

Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor that in humans is encoded by the PPARG gene.[5][6][7]

Tissue distribution

PPARG is mainly present in adipose tissue, colon and macrophages. Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine).[8]


PPARG regulates fatty acid storage and glucose metabolism. The genes activated by PPARG stimulate lipid uptake and adipogenesis by fat cells. PPARG knockout mice fail to generate adipose tissue when fed a high-fat diet.[9]

This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Alternatively spliced transcript variants that encode different isoforms have been described.[10]

Many naturally occurring agents directly bind with and activate PPAR gamma. These agents include various polyunsaturated fatty acids like arachidonic acid and arachidonic acid metabolites such as certain members of the 5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid family, e.g. 5-oxo-15(S)-HETE and 5-oxo-ETE or 15-Hydroxyicosatetraenoic acid family including 15(S)-HETE, 15(R)-HETE, and 15(S)-HpETE.[11][12][13] The activation of PPAR gamma by these and other ligands may be responsible for inhibiting the growth of cultured human breast, gastric, lung, prostate and other cancer cell lines.[14]


Peroxisome proliferator-activated receptor gamma has been shown to interact with:

Clinical relevance

PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancer. PPAR-gamma agonists have been used in the treatment of hyperlipidaemia and hyperglycemia.[25] PPAR-gamma decreases the inflammatory response of many cardiovascular cells, particularly endothelial cells.[26] PPAR-gamma activates the PON1 gene, increasing synthesis and release of paraoxonase 1 from the liver, reducing atherosclerosis.[27]

Many insulin sensitizing drugs (namely, the thiazolidinediones) used in the treatment of diabetes target PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion. Different classes of compounds which activate PPARgamma weaker than thiazolidinediones (the so-called “partial agonists of PPARgamma”) are currently studied with the hope that such compounds would be still effective hypoglycaemic agents but with fewer side effects.[28][29]

A fusion protein of PPAR-γ1 and the thyroid transcription factor PAX8 is present in approximately one-third of follicular thyroid carcinomas, to be specific those cancers with a chromosomal translocation of t(2;3)(q13;p25), which permits juxtaposition of portions of both genes.[30][31]


  1. "Diseases that are genetically associated with PPARG view/edit references on wikidata".
  2. "Drugs that physically interact with Peroxisome proliferator-activated receptor gamma view/edit references on wikidata".
  3. "Human PubMed Reference:".
  4. "Mouse PubMed Reference:".
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  19. 1 2 3 4 Kodera Y, Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S (October 2000). "Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators". J. Biol. Chem. 275 (43): 33201–4. doi:10.1074/jbc.C000517200. PMID 10944516.
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  22. Nishizawa H, Yamagata K, Shimomura I, Takahashi M, Kuriyama H, Kishida K, Hotta K, Nagaretani H, Maeda N, Matsuda M, Kihara S, Nakamura T, Nishigori H, Tomura H, Moore DD, Takeda J, Funahashi T, Matsuzawa Y (January 2002). "Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation". J. Biol. Chem. 277 (2): 1586–92. doi:10.1074/jbc.M104301200. PMID 11696534.
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  25. Li Y, Qi Y, Huang TH, Yamahara J, Roufogalis BD (January 2008). "Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-alpha/-gamma activator properties". Diabetes Obes Metab. 10 (1): 10–7. doi:10.1111/j.1463-1326.2007.00708.x. PMID 18095947.
  26. Hamblin M, Chang L, Fan Y, Zhang J, Chen YE (June 2009). "PPARs and the Cardiovascular System". Antioxid. Redox Signal. 11 (6): 1415–52. doi:10.1089/ARS.2008.2280. PMC 2737093Freely accessible. PMID 19061437.
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  28. Atanasov AG, Wang JN, Gu SP, Bu J, Kramer MP, Baumgartner L, Fakhrudin N, Ladurner A, Malainer C, Vuorinen A, Noha SM, Schwaiger S, Rollinger JM, Schuster D, Stuppner H, Dirsch VM, Heiss EH (2013). "Honokiol: a non-adipogenic PPARγ agonist from nature". Biochim. Biophys. Acta. 1830 (10): 4813–9. doi:10.1016/j.bbagen.2013.06.021. PMC 3790966Freely accessible. PMID 23811337.
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Further reading

  • Qi C, Zhu Y, Reddy JK (2001). "Peroxisome proliferator-activated receptors, coactivators, and downstream targets". Cell Biochem. Biophys. 32 Spring: 187–204. PMID 11330046. 
  • Kadowaki T, Hara K, Kubota N, Tobe K, Terauchi Y, Yamauchi T, Eto K, Kadowaki H, Noda M, Hagura R, Akanuma Y (2002). "The role of PPARgamma in high-fat diet-induced obesity and insulin resistance". J. Diabetes Complicat. 16 (1): 41–5. doi:10.1016/S1056-8727(01)00206-9. PMID 11872365. 
  • Wakino S, Law RE, Hsueh WA (2002). "Vascular protective effects by activation of nuclear receptor PPARgamma". J. Diabetes Complicat. 16 (1): 46–9. doi:10.1016/S1056-8727(01)00197-0. PMID 11872366. 
  • Takano H, Komuro I (2002). "Roles of peroxisome proliferator-activated receptor gamma in cardiovascular disease". J. Diabetes Complicat. 16 (1): 108–14. doi:10.1016/S1056-8727(01)00203-3. PMID 11872377. 
  • Stumvoll M, Häring H (2002). "The peroxisome proliferator-activated receptor-gamma2 Pro12Ala polymorphism". Diabetes. 51 (8): 2341–7. doi:10.2337/diabetes.51.8.2341. PMID 12145143. 
  • Koeffler HP (2003). "Peroxisome proliferator-activated receptor gamma and cancers". Clin. Cancer Res. 9 (1): 1–9. PMID 12538445. 
  • Puigserver P, Spiegelman BM (2003). "Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator". Endocr. Rev. 24 (1): 78–90. doi:10.1210/er.2002-0012. PMID 12588810. 
  • Takano H, Hasegawa H, Nagai T, Komuro I (2003). "The role of PPARgamma-dependent pathway in the development of cardiac hypertrophy". Drugs Today. 39 (5): 347–57. doi:10.1358/dot.2003.39.5.799458. PMID 12861348. 
  • Rangwala SM, Lazar MA (2004). "Peroxisome proliferator-activated receptor gamma in diabetes and metabolism". Trends Pharmacol. Sci. 25 (6): 331–6. doi:10.1016/ PMID 15165749. 
  • Cuzzocrea S (2005). "Peroxisome proliferator-activated receptors gamma ligands and ischemia and reperfusion injury". Vascul. Pharmacol. 41 (6): 187–95. doi:10.1016/j.vph.2004.10.004. PMID 15653094. 
  • Savage DB (2007). "PPAR gamma as a metabolic regulator: insights from genomics and pharmacology". Expert Reviews in Molecular Medicine. 7 (1): 1–16. doi:10.1017/S1462399405008793. PMID 15673477. 
  • Pégorier JP (2005). "[PPAR receptors and insulin sensitivity: new agonists in development]". Ann. Endocrinol. (Paris). 66 (2 Pt 2): 1S10–7. PMID 15959400. 
  • Tsai YS, Maeda N (2005). "PPARgamma: a critical determinant of body fat distribution in humans and mice". Trends Cardiovasc. Med. 15 (3): 81–5. doi:10.1016/j.tcm.2005.04.002. PMID 16039966. 
  • Gurnell M (2006). "Peroxisome proliferator-activated receptor gamma and the regulation of adipocyte function: lessons from human genetic studies". Best Pract. Res. Clin. Endocrinol. Metab. 19 (4): 501–23. doi:10.1016/j.beem.2005.10.001. PMID 16311214. 
  • Cecil JE, Watt P, Palmer CN, Hetherington M (2006). "Energy balance and food intake: the role of PPARgamma gene polymorphisms". Physiol. Behav. 88 (3): 227–33. doi:10.1016/j.physbeh.2006.05.028. PMID 16777151. 
  • Rousseaux C, Desreumaux P (2007). "[The peroxisome-proliferator-activated gamma receptor and chronic inflammatory bowel disease (PPARgamma and IBD)]". J. Soc. Biol. 200 (2): 121–31. doi:10.1051/jbio:2006015. PMID 17151549. 
  • Eriksson JG (2007). "Gene polymorphisms, size at birth, and the development of hypertension and type 2 diabetes". J. Nutr. 137 (4): 1063–5. PMID 17374678. 
  • Tönjes A, Stumvoll M (2007). "The role of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma in diabetes risk". Current opinion in clinical nutrition and metabolic care. 10 (4): 410–4. doi:10.1097/MCO.0b013e3281e389d9. PMID 17563457. 
  • Burgermeister E, Seger R (2007). "MAPK kinases as nucleo-cytoplasmic shuttles for PPARgamma". Cell Cycle. 6 (13): 1539–48. doi:10.4161/cc.6.13.4453. PMID 17611413. 
  • Papageorgiou E, Pitulis N, Msaouel P, Lembessis P, Koutsilieris M (2007). "The non-genomic crosstalk between PPAR-gamma ligands and ERK1/2 in cancer cell lines". Expert Opin. Ther. Targets. 11 (8): 1071–85. doi:10.1517/14728222.11.8.1071. PMID 17665979. 

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