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Peroxisome proliferator-activated receptor gamma: Wikis


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Peroxisome proliferator-activated receptor gamma

PDB rendering based on 1fm6.
Available structures
1fm6, 1fm9, 1i7i, 1k74, 1knu, 1nyx, 1prg, 1rdt, 1wm0, 1zeo, 1zgy, 2ath, 2f4b, 2fvj, 2g0g, 2g0h, 2gtk, 2hfp, 2i4j, 2i4p, 2i4z, 2om9, 2prg, 3prg, 4prg
External IDs OMIM601487 MGI97747 HomoloGene7899 GeneCards: PPARG Gene
RNA expression pattern
PBB GE PPARG 208510 s at tn.png
More reference expression data
Species Human Mouse
Entrez 5468 19016
Ensembl ENSG00000132170 ENSMUSG00000000440
UniProt P37231 A0N0C8
RefSeq (mRNA) NM_005037 NM_011146
RefSeq (protein) NP_005028 NP_035276
Location (UCSC) Chr 3:
12.3 - 12.45 Mb
Chr 6:
115.39 - 115.46 Mb
PubMed search [1] [2]

Peroxisome proliferator-activated receptor gamma (PPAR-gamma 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.[1][2]



PPARG regulates fatty acid storage and glucose metabolism. Many insulin sensitizing drugs used in the treatment of diabetes target PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion. 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.[3]

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. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described.[4]


Peroxisome proliferator-activated receptor gamma has been shown to interact with MED1,[5] PPARGC1A,[6][7] Nuclear receptor coactivator 3,[5] Retinoblastoma protein,[8] NCOA4,[9] EP300,[8][5] HDAC3,[10][8] Nuclear receptor coactivator 2,[5] EDF1,[11] Retinoid X receptor alpha[12][13][14] and Small heterodimer partner.[15]


  1. ^ Greene ME, Blumberg B, McBride OW, Yi HF, Kronquist K, Kwan K, Hsieh L, Greene G, Nimer SD (1995). "Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping". Gene Expr. 4 (4-5): 281–99. PMID 7787419.  
  2. ^ Elbrecht A, Chen Y, Cullinan CA, Hayes N, Leibowitz M, Moller DE, Berger J (July 1996). "Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2". Biochem. Biophys. Res. Commun. 224 (2): 431–7. doi:10.1006/bbrc.1996.1044. PMID 8702406.  
  3. ^ Jones JR, Barrick C, Kim KA, Lindner J, Blondeau B, Fujimoto Y, Shiota M, Kesterson RA, Kahn BB, Magnuson MA (April 2005). "Deletion of PPARgamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance". Proc. Natl. Acad. Sci. U.S.A. 102 (17): 6207–12. doi:10.1073/pnas.0306743102. PMID 15833818.  
  4. ^ "Entrez Gene: PPARG peroxisome proliferator-activated receptor gamma".  
  5. ^ a b c d Kodera, Y; Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S (Oct. 2000). "Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators". J. Biol. Chem. (UNITED STATES) 275 (43): 33201–4. doi:10.1074/jbc.C000517200. ISSN 0021-9258. PMID 10944516.  
  6. ^ Wallberg, Annika E; Yamamura Soichiro, Malik Sohail, Spiegelman Bruce M, Roeder Robert G (Nov. 2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Mol. Cell (United States) 12 (5): 1137–49. ISSN 1097-2765. PMID 14636573.  
  7. ^ Puigserver, P; Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman B M (Nov. 1999). "Activation of PPARgamma coactivator-1 through transcription factor docking". Science (UNITED STATES) 286 (5443): 1368–71. ISSN 0036-8075. PMID 10558993.  
  8. ^ a b c Fajas, Lluis; Egler Viviane, Reiter Raphael, Hansen Jacob, Kristiansen Karsten, Debril Marie-Bernard, Miard Stéphanie, Auwerx Johan (Dec. 2002). "The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation". Dev. Cell (United States) 3 (6): 903–10. ISSN 1534-5807. PMID 12479814.  
  9. ^ Heinlein, C A; Ting H J, Yeh S, Chang C (Jun. 1999). "Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma". J. Biol. Chem. (UNITED STATES) 274 (23): 16147–52. ISSN 0021-9258. PMID 10347167.  
  10. ^ Franco, Peter J; Li Guangjin, Wei Li-Na (Aug. 2003). "Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase". Mol. Cell. Endocrinol. (Ireland) 206 (1-2): 1–12. ISSN 0303-7207. PMID 12943985.  
  11. ^ Brendel, Carole; Gelman Laurent, Auwerx Johan (Jun. 2002). "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Mol. Endocrinol. (United States) 16 (6): 1367–77. ISSN 0888-8809. PMID 12040021.  
  12. ^ Tontonoz, P; Graves R A, Budavari A I, Erdjument-Bromage H, Lui M, Hu E, Tempst P, Spiegelman B M (Dec. 1994). "Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha". Nucleic Acids Res. (ENGLAND) 22 (25): 5628–34. ISSN 0305-1048. PMID 7838715.  
  13. ^ Berger, J; Patel H V, Woods J, Hayes N S, Parent S A, Clemas J, Leibowitz M D, Elbrecht A, Rachubinski R A, Capone J P, Moller D E (Apr. 2000). "A PPARgamma mutant serves as a dominant negative inhibitor of PPAR signaling and is localized in the nucleus". Mol. Cell. Endocrinol. (IRELAND) 162 (1-2): 57–67. ISSN 0303-7207. PMID 10854698.  
  14. ^ Gampe, R T; Montana V G, Lambert M H, Miller A B, Bledsoe R K, Milburn M V, Kliewer S A, Willson T M, Xu H E (Mar. 2000). "Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors". Mol. Cell (UNITED STATES) 5 (3): 545–55. ISSN 1097-2765. PMID 10882139.  
  15. ^ Nishizawa, Hitoshi; Yamagata Kazuya, Shimomura Iichiro, Takahashi Masahiko, Kuriyama Hiroshi, Kishida Ken, Hotta Kikuko, Nagaretani Hiroyuki, Maeda Norikazu, Matsuda Morihiro, Kihara Shinji, Nakamura Tadashi, Nishigori Hidekazu, Tomura Hideaki, Moore David D, Takeda Jun, Funahashi Tohru, Matsuzawa Yuji (Jan. 2002). "Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation". J. Biol. Chem. (United States) 277 (2): 1586–92. doi:10.1074/jbc.M104301200. ISSN 0021-9258. PMID 11696534.  

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, et al. (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. PMID 17611413.  
  • Papageorgiou E, Pitulis N, Msaouel P, et al. (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.  

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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