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Gene Review

Pparg  -  peroxisome proliferator activated receptor...

Mus musculus

Synonyms: Nr1c3, Nuclear receptor subfamily 1 group C member 3, PPAR-gamma, PPAR-gamma2, PPARgamma, ...
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Disease relevance of Pparg


High impact information on Pparg


Psychiatry related information on Pparg


Chemical compound and disease context of Pparg


Biological context of Pparg


Anatomical context of Pparg


Associations of Pparg with chemical compounds

  • Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor selectively activated by ligands of the thiazolidinedione class [23].
  • Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux [22].
  • We demonstrated that Insig-1 is regulated by peroxisome proliferator-activated receptor gamma (PPARgamma) providing a link between insulin sensitization/glucose homeostasis and lipid homeostasis [25].
  • Using an experimental murine model of LC migration induced by TNF-alpha, we show that the highly potent PPAR gamma agonist rosiglitazone specifically impairs the departure of LCs from the epidermis [13].
  • To determine whether increased PPAR-gamma expression in the liver has any functional consequences, we examined the effect of troglitazone treatment on the hepatic mRNA levels of several PPAR-gamma-responsive adipose tissue-specific genes that have either no detectable or very low basal expression in the liver [14].
  • Our results demonstrated that PPARgamma is required to maintain normal adiposity and insulin sensitivity in adult mice [26].
  • These findings reveal an essential role of PPAR gamma in macrophages for the maintenance of whole-body insulin action and in mediating the antidiabetic actions of TZDs [27].
  • Both pioglitazone and ciglitazone (PPARgamma agonists; 0.5-5.0 microg, intracerebroventricularly (i.c.v.), once daily) prevented the expression of behavioral sensitization to METH challenge on withdrawal day 7, but not the sensitization that occurred during repeated administration of METH [28].
  • PPARgamma activation by rosiglitazone prevented the mitochondrial dysfunction and oxidative stress that occurred when mutant striatal cells were challenged with pathological increases in calcium [29].
  • Although these modifications were also found in TNFalpha-treated adipocytes, rosiglitazone and 9-cis retinoic acid (PPARgamma and RXR ligands) were unable to prevent triglyceride loss in FCCP-treated cells [30].
  • The innate FoxO1 transrepression function enables insulin to augment PPARgamma activity, which in turn leads to insulin sensitization, and this feed-forward cycle represents positive reinforcing connections between insulin and PPARgamma signaling [31].

Physical interactions of Pparg


Regulatory relationships of Pparg


Other interactions of Pparg


Analytical, diagnostic and therapeutic context of Pparg


  1. Genetic deficiency in Pparg does not alter development of experimental prostate cancer. Saez, E., Olson, P., Evans, R.M. Nat. Med. (2003) [Pubmed]
  2. Regulation of PPAR gamma gene expression by nutrition and obesity in rodents. Vidal-Puig, A., Jimenez-Liñan, M., Lowell, B.B., Hamann, A., Hu, E., Spiegelman, B., Flier, J.S., Moller, D.E. J. Clin. Invest. (1996) [Pubmed]
  3. Activation of PPAR gamma and delta by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Bassaganya-Riera, J., Reynolds, K., Martino-Catt, S., Cui, Y., Hennighausen, L., Gonzalez, F., Rohrer, J., Benninghoff, A.U., Hontecillas, R. Gastroenterology (2004) [Pubmed]
  4. Peroxisome proliferator-activated receptor-gamma agonist 15-deoxy-Delta(12,14)-prostaglandin J(2) ameliorates experimental autoimmune encephalomyelitis. Diab, A., Deng, C., Smith, J.D., Hussain, R.Z., Phanavanh, B., Lovett-Racke, A.E., Drew, P.D., Racke, M.K. J. Immunol. (2002) [Pubmed]
  5. Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Zhao, X., Sun, G., Zhang, J., Strong, R., Song, W., Gonzales, N., Grotta, J.C., Aronowski, J. Ann. Neurol. (2007) [Pubmed]
  6. Peroxisome proliferator-activated receptor gamma is required for regulatory CD4+ T cell-mediated protection against colitis. Hontecillas, R., Bassaganya-Riera, J. J. Immunol. (2007) [Pubmed]
  7. Importance of peroxisome proliferator-activated receptor-gamma in hepatic ischemia/reperfusion injury in mice. Akahori, T., Sho, M., Hamada, K., Suzaki, Y., Kuzumoto, Y., Nomi, T., Nakamura, S., Enomoto, K., Kanehiro, H., Nakajima, Y. J. Hepatol. (2007) [Pubmed]
  8. Hyperglycemia enhances adipogenic induction of lipid accumulation: involvement of extracellular signal-regulated protein kinase 1/2, phosphoinositide 3-kinase/Akt, and peroxisome proliferator-activated receptor gamma signaling. Chuang, C.C., Yang, R.S., Tsai, K.S., Ho, F.M., Liu, S.H. Endocrinology (2007) [Pubmed]
  9. IL-13 attenuates gastrointestinal candidiasis in normal and immunodeficient RAG-2(-/-) mice via peroxisome proliferator-activated receptor-gamma activation. Coste, A., Lagane, C., Filipe, C., Authier, H., Galès, A., Bernad, J., Douin-Echinard, V., Lepert, J.C., Balard, P., Linas, M.D., Arnal, J.F., Auwerx, J., Pipy, B. J. Immunol. (2008) [Pubmed]
  10. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Kliewer, S.A., Lenhard, J.M., Willson, T.M., Patel, I., Morris, D.C., Lehmann, J.M. Cell (1995) [Pubmed]
  11. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Forman, B.M., Tontonoz, P., Chen, J., Brun, R.P., Spiegelman, B.M., Evans, R.M. Cell (1995) [Pubmed]
  12. Adipose tissue integrity as a prerequisite for systemic energy balance: a critical role for peroxisome proliferator-activated receptor gamma. Anghel, S.I., Bedu, E., Vivier, C.D., Descombes, P., Desvergne, B., Wahli, W. J. Biol. Chem. (2007) [Pubmed]
  13. Peroxisome proliferator-activated receptor gamma inhibits the migration of dendritic cells: consequences for the immune response. Angeli, V., Hammad, H., Staels, B., Capron, M., Lambrecht, B.N., Trottein, F. J. Immunol. (2003) [Pubmed]
  14. Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice. Memon, R.A., Tecott, L.H., Nonogaki, K., Beigneux, A., Moser, A.H., Grunfeld, C., Feingold, K.R. Endocrinology (2000) [Pubmed]
  15. Weight-loss-associated induction of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice. Verreth, W., De Keyzer, D., Pelat, M., Verhamme, P., Ganame, J., Bielicki, J.K., Mertens, A., Quarck, R., Benhabilès, N., Marguerie, G., Mackness, B., Mackness, M., Ninio, E., Herregods, M.C., Balligand, J.L., Holvoet, P. Circulation (2004) [Pubmed]
  16. The peroxisome proliferator-activated receptor gamma ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency. Lytle, C., Tod, T.J., Vo, K.T., Lee, J.W., Atkinson, R.D., Straus, D.S. Inflamm. Bowel Dis. (2005) [Pubmed]
  17. PPAR-gamma overexpression suppresses glucose-induced proinsulin biosynthesis and insulin release synergistically with pioglitazone in MIN6 cells. Nakamichi, Y., Kikuta, T., Ito, E., Ohara-Imaizumi, M., Nishiwaki, C., Ishida, H., Nagamatsu, S. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  18. Vasoactive hormone adrenomedullin and its binding protein: anti-inflammatory effects by up-regulating peroxisome proliferator-activated receptor-gamma. Miksa, M., Wu, R., Cui, X., Dong, W., Das, P., Simms, H.H., Ravikumar, T.S., Wang, P. J. Immunol. (2007) [Pubmed]
  19. Loss of peroxisome proliferator-activated receptor gamma in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis. Kapoor, M., McCann, M., Liu, S., Huh, K., Denton, C.P., Abraham, D.J., Leask, A. Arthritis Rheum. (2009) [Pubmed]
  20. Muscle-specific Pparg deletion causes insulin resistance. Hevener, A.L., He, W., Barak, Y., Le, J., Bandyopadhyay, G., Olson, P., Wilkes, J., Evans, R.M., Olefsky, J. Nat. Med. (2003) [Pubmed]
  21. MSX2 promotes osteogenesis and suppresses adipogenic differentiation of multipotent mesenchymal progenitors. Cheng, S.L., Shao, J.S., Charlton-Kachigian, N., Loewy, A.P., Towler, D.A. J. Biol. Chem. (2003) [Pubmed]
  22. Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Akiyama, T.E., Sakai, S., Lambert, G., Nicol, C.J., Matsusue, K., Pimprale, S., Lee, Y.H., Ricote, M., Glass, C.K., Brewer, H.B., Gonzalez, F.J. Mol. Cell. Biol. (2002) [Pubmed]
  23. Cyclin D1 repression of peroxisome proliferator-activated receptor gamma expression and transactivation. Wang, C., Pattabiraman, N., Zhou, J.N., Fu, M., Sakamaki, T., Albanese, C., Li, Z., Wu, K., Hulit, J., Neumeister, P., Novikoff, P.M., Brownlee, M., Scherer, P.E., Jones, J.G., Whitney, K.D., Donehower, L.A., Harris, E.L., Rohan, T., Johns, D.C., Pestell, R.G. Mol. Cell. Biol. (2003) [Pubmed]
  24. Troglitazone regulates peroxisome proliferator-activated receptors and inducible nitric oxide synthase in murine ovarian macrophages. Minge, C.E., Ryan, N.K., Van Der Hoek, K.H., Robker, R.L., Norman, R.J. Biol. Reprod. (2006) [Pubmed]
  25. Rosiglitazone induction of Insig-1 in white adipose tissue reveals a novel interplay of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein in the regulation of adipogenesis. Kast-Woelbern, H.R., Dana, S.L., Cesario, R.M., Sun, L., de Grandpre, L.Y., Brooks, M.E., Osburn, D.L., Reifel-Miller, A., Klausing, K., Leibowitz, M.D. J. Biol. Chem. (2004) [Pubmed]
  26. Hypotension, lipodystrophy, and insulin resistance in generalized PPARgamma-deficient mice rescued from embryonic lethality. Duan, S.Z., Ivashchenko, C.Y., Whitesall, S.E., D'Alecy, L.G., Duquaine, D.C., Brosius, F.C., Gonzalez, F.J., Vinson, C., Pierre, M.A., Milstone, D.S., Mortensen, R.M. J. Clin. Invest. (2007) [Pubmed]
  27. Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. Hevener, A.L., Olefsky, J.M., Reichart, D., Nguyen, M.T., Bandyopadyhay, G., Leung, H.Y., Watt, M.J., Benner, C., Febbraio, M.A., Nguyen, A.K., Folian, B., Subramaniam, S., Gonzalez, F.J., Glass, C.K., Ricote, M. J. Clin. Invest. (2007) [Pubmed]
  28. Peroxisome proliferator-activated receptor gamma activation relieves expression of behavioral sensitization to methamphetamine in mice. Maeda, T., Kiguchi, N., Fukazawa, Y., Yamamoto, A., Ozaki, M., Kishioka, S. Neuropsychopharmacology (2007) [Pubmed]
  29. Rosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells: possible role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the pathogenesis of Huntington disease. Quintanilla, R.A., Jin, Y.N., Fuenzalida, K., Bronfman, M., Johnson, G.V. J. Biol. Chem. (2008) [Pubmed]
  30. Mild mitochondrial uncoupling induces 3T3-L1 adipocyte de-differentiation by a PPARgamma-independent mechanism, whereas TNFalpha-induced de-differentiation is PPARgamma dependent. Tejerina, S., De Pauw, A., Vankoningsloo, S., Houbion, A., Renard, P., De Longueville, F., Raes, M., Arnould, T. J. Cell. Sci. (2009) [Pubmed]
  31. FOXO1 transrepresses peroxisome proliferator-activated receptor gamma transactivation, coordinating an insulin-induced feed-forward response in adipocytes. Fan, W., Imamura, T., Sonoda, N., Sears, D.D., Patsouris, D., Kim, J.J., Olefsky, J.M. J. Biol. Chem. (2009) [Pubmed]
  32. Activation of peroxisome proliferator-activated receptor-gamma inhibits differentiation of preosteoblasts. Khan, E., Abu-Amer, Y. J. Lab. Clin. Med. (2003) [Pubmed]
  33. An intact DNA-binding domain is not required for peroxisome proliferator-activated receptor gamma (PPARgamma) binding and activation on some PPAR response elements. Temple, K.A., Cohen, R.N., Wondisford, S.R., Yu, C., Deplewski, D., Wondisford, F.E. J. Biol. Chem. (2005) [Pubmed]
  34. Peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein alpha, and cell cycle status regulate the commitment to adipocyte differentiation. Shao, D., Lazar, M.A. J. Biol. Chem. (1997) [Pubmed]
  35. Regulation of Wnt signaling during adipogenesis. Bennett, C.N., Ross, S.E., Longo, K.A., Bajnok, L., Hemati, N., Johnson, K.W., Harrison, S.D., MacDougald, O.A. J. Biol. Chem. (2002) [Pubmed]
  36. Essential role of citrate export from mitochondria at early differentiation stage of 3T3-L1 cells for their effective differentiation into fat cells, as revealed by studies using specific inhibitors of mitochondrial di- and tricarboxylate carriers. Kajimoto, K., Terada, H., Baba, Y., Shinohara, Y. Mol. Genet. Metab. (2005) [Pubmed]
  37. Peroxisome proliferator-activated receptor gamma controls Muc1 transcription in trophoblasts. Shalom-Barak, T., Nicholas, J.M., Wang, Y., Zhang, X., Ong, E.S., Young, T.H., Gendler, S.J., Evans, R.M., Barak, Y. Mol. Cell. Biol. (2004) [Pubmed]
  38. Activation of peroxisome proliferator-activated receptor-gamma inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts. Jeon, M.J., Kim, J.A., Kwon, S.H., Kim, S.W., Park, K.S., Park, S.W., Kim, S.Y., Shin, C.S. J. Biol. Chem. (2003) [Pubmed]
  39. Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice. Patel, D.D., Knight, B.L., Wiggins, D., Humphreys, S.M., Gibbons, G.F. J. Lipid Res. (2001) [Pubmed]
  40. The peroxisome proliferator-activated receptor gamma regulates expression of the perilipin gene in adipocytes. Arimura, N., Horiba, T., Imagawa, M., Shimizu, M., Sato, R. J. Biol. Chem. (2004) [Pubmed]
  41. Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat. Lazarenko, O.P., Rzonca, S.O., Suva, L.J., Lecka-Czernik, B. Bone (2006) [Pubmed]
  42. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists. Nawrocki, A.R., Rajala, M.W., Tomas, E., Pajvani, U.B., Saha, A.K., Trumbauer, M.E., Pang, Z., Chen, A.S., Ruderman, N.B., Chen, H., Rossetti, L., Scherer, P.E. J. Biol. Chem. (2006) [Pubmed]
  43. Reciprocal roles of MSX2 in regulation of osteoblast and adipocyte differentiation. Ichida, F., Nishimura, R., Hata, K., Matsubara, T., Ikeda, F., Hisada, K., Yatani, H., Cao, X., Komori, T., Yamaguchi, A., Yoneda, T. J. Biol. Chem. (2004) [Pubmed]
  44. Differential expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) and its coactivators steroid receptor coactivator-1 and PPAR-binding protein PBP in the brown fat, urinary bladder, colon, and breast of the mouse. Jain, S., Pulikuri, S., Zhu, Y., Qi, C., Kanwar, Y.S., Yeldandi, A.V., Rao, M.S., Reddy, J.K. Am. J. Pathol. (1998) [Pubmed]
  45. Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-gamma. Dalen, K.T., Schoonjans, K., Ulven, S.M., Weedon-Fekjaer, M.S., Bentzen, T.G., Koutnikova, H., Auwerx, J., Nebb, H.I. Diabetes (2004) [Pubmed]
  46. Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in mice. Gray, S.L., Nora, E.D., Grosse, J., Manieri, M., Stoeger, T., Medina-Gomez, G., Burling, K., Wattler, S., Russ, A., Yeo, G.S., Chatterjee, V.K., O'Rahilly, S., Voshol, P.J., Cinti, S., Vidal-Puig, A. Diabetes (2006) [Pubmed]
  47. Peroxisome proliferator-activated receptor gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis. Fuenzalida, K., Quintanilla, R., Ramos, P., Piderit, D., Fuentealba, R.A., Martinez, G., Inestrosa, N.C., Bronfman, M. J. Biol. Chem. (2007) [Pubmed]
  48. Tissue-selective, bidirectional regulation of PEX11 alpha and perilipin genes through a common peroxisome proliferator response element. Shimizu, M., Takeshita, A., Tsukamoto, T., Gonzalez, F.J., Osumi, T. Mol. Cell. Biol. (2004) [Pubmed]
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