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Gene Review

Ppara  -  peroxisome proliferator activated receptor...

Mus musculus

Synonyms: 4933429D07Rik, AI118064, AW742785, Nr1c1, Nuclear receptor subfamily 1 group C member 1, ...
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Disease relevance of Ppara


Psychiatry related information on Ppara

  • Our results, which show that OEA induces satiety by activating PPAR-alpha, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders [6].
  • Treatment of alcohol-fed mice with a PPARalpha agonist reverses fatty liver despite continued alcohol consumption [7].

High impact information on Ppara


Chemical compound and disease context of Ppara


Biological context of Ppara

  • Hepatic gluconeogenic gene expression was increased and insulin-mediated suppression of endogenous glucose production was less effective in dexamethasone-treated Ppara+/+ mice [1].
  • Furthermore, Ppara-deficient mice exhibited sustained WAT inflammation during CL treatment, indicating that upregulation of Ppara limits proinflammatory signaling during chronic lipolytic activation [17].
  • Histological, physiological, and molecular analysis of CL-induced remodeling in wild-type mice and mice lacking Ppara demonstrated that Ppara was important for inducing adipocyte mitochondrial biogenesis and upregulating genes involved in fatty acid oxidation [17].
  • These results identify hepatic activation of PPAR-alpha as a mechanism underlying glucocorticoid-induced insulin resistance [1].
  • Differential activation of adipogenesis by multiple PPAR isoforms [18].

Anatomical context of Ppara

  • Ovulatory human chorionic gonadotropin downregulated expression of Pparg and Ppara in EMR1+ ovarian macrophages, but no hormonal responsiveness was observed in H2+ cells [19].
  • Isolation of immune cells (EMR1+ or H2+) showed that Pparg and Ppara were expressed in ovarian macrophages at much higher levels than in peritoneal macrophages [19].
  • Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma [20].
  • We tested whether fasting-associated fatty acid release from adipose tissues alters hepatic transporter expression and bile formation in a PPARalpha-dependent manner [21].
  • These data suggest that tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, is in part a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms [22].

Associations of Ppara with chemical compounds


Physical interactions of Ppara


Regulatory relationships of Ppara

  • These results suggest that in the adult rodent heart, UCP-3 expression is regulated by PPARalpha [32].
  • In conclusion, PPARalpha activation stimulates hepatic MTP expression via increased transcription of the Mtp gene [33].
  • When challenged with a peroxisome proliferator, L-PBE-/- mice showed increases in the levels of hepatic mRNAs and proteins that are regulated by PPARalpha except for appreciable blunting of peroxisome proliferative response as compared with that observed in hepatocytes of wild type mice similarly treated [34].
  • These results demonstrate that the FATP gene possesses a functional PPRE and is up-regulated by activators of PPARalpha and PPARgamma, thereby linking the activity of the protein to the expression of its gene [28].
  • Under these conditions, hepatic PPAR gamma expression increased in both the control and PPAR alpha-deficient mice [35].

Other interactions of Ppara


Analytical, diagnostic and therapeutic context of Ppara


  1. Dexamethasone induction of hypertension and diabetes is PPAR-alpha dependent in LDL receptor-null mice. Bernal-Mizrachi, C., Weng, S., Feng, C., Finck, B.N., Knutsen, R.H., Leone, T.C., Coleman, T., Mecham, R.P., Kelly, D.P., Semenkovich, C.F. Nat. Med. (2003) [Pubmed]
  2. Genetic deficiency in Pparg does not alter development of experimental prostate cancer. Saez, E., Olson, P., Evans, R.M. Nat. Med. (2003) [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. In vivo activation of PPAR target genes by RXR homodimers. IJpenberg, A., Tan, N.S., Gelman, L., Kersten, S., Seydoux, J., Xu, J., Metzger, D., Canaple, L., Chambon, P., Wahli, W., Desvergne, B. EMBO J. (2004) [Pubmed]
  5. Systemic and distal repercussions of liver-specific peroxisome proliferator-activated receptor-alpha control of the acute-phase response. Mansouri, R.M., Baugé, E., Staels, B., Gervois, P. Endocrinology (2008) [Pubmed]
  6. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Fu, J., Gaetani, S., Oveisi, F., Lo Verme, J., Serrano, A., Rodríguez De Fonseca, F., Rosengarth, A., Luecke, H., Di Giacomo, B., Tarzia, G., Piomelli, D. Nature (2003) [Pubmed]
  7. Alcohol Deranges Hepatic Lipid Metabolism via Altered Transcriptional Regulation. Crabb, D.W. Trans. Am. Clin. Climatol. Assoc. (2004) [Pubmed]
  8. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Wang, Y.X., Lee, C.H., Tiep, S., Yu, R.T., Ham, J., Kang, H., Evans, R.M. Cell (2003) [Pubmed]
  9. 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]
  10. PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3. Koo, S.H., Satoh, H., Herzig, S., Lee, C.H., Hedrick, S., Kulkarni, R., Evans, R.M., Olefsky, J., Montminy, M. Nat. Med. (2004) [Pubmed]
  11. Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis. Ge, K., Guermah, M., Yuan, C.X., Ito, M., Wallberg, A.E., Spiegelman, B.M., Roeder, R.G. Nature (2002) [Pubmed]
  12. Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by peroxisome proliferator-activated receptor ligands. Niho, N., Takahashi, M., Kitamura, T., Shoji, Y., Itoh, M., Noda, T., Sugimura, T., Wakabayashi, K. Cancer Res. (2003) [Pubmed]
  13. Diverse regulation of NF-kappaB and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver. Romics, L., Kodys, K., Dolganiuc, A., Graham, L., Velayudham, A., Mandrekar, P., Szabo, G. Hepatology (2004) [Pubmed]
  14. Peroxisome proliferator-activated receptor alpha (PPARalpha) agonist treatment reverses PPARalpha dysfunction and abnormalities in hepatic lipid metabolism in ethanol-fed mice. Fischer, M., You, M., Matsumoto, M., Crabb, D.W. J. Biol. Chem. (2003) [Pubmed]
  15. 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]
  16. Peroxisome proliferator-activated receptor-alpha and retinoid X receptor agonists inhibit inflammatory responses of astrocytes. Xu, J., Chavis, J.A., Racke, M.K., Drew, P.D. J. Neuroimmunol. (2006) [Pubmed]
  17. Metabolic and cellular plasticity in white adipose tissue II: role of peroxisome proliferator-activated receptor-alpha. Li, P., Zhu, Z., Lu, Y., Granneman, J.G. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  18. Differential activation of adipogenesis by multiple PPAR isoforms. Brun, R.P., Tontonoz, P., Forman, B.M., Ellis, R., Chen, J., Evans, R.M., Spiegelman, B.M. Genes Dev. (1996) [Pubmed]
  19. 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]
  20. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma. Li, A.C., Binder, C.J., Gutierrez, A., Brown, K.K., Plotkin, C.R., Pattison, J.W., Valledor, A.F., Davis, R.A., Willson, T.M., Witztum, J.L., Palinski, W., Glass, C.K. J. Clin. Invest. (2004) [Pubmed]
  21. Induction of hepatic ABC transporter expression is part of the PPARalpha-mediated fasting response in the mouse. Kok, T., Wolters, H., Bloks, V.W., Havinga, R., Jansen, P.L., Staels, B., Kuipers, F. Gastroenterology (2003) [Pubmed]
  22. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Kliewer, S.A., Forman, B.M., Blumberg, B., Ong, E.S., Borgmeyer, U., Mangelsdorf, D.J., Umesono, K., Evans, R.M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  23. PPAR alpha is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue. Lee, Y., Yu, X., Gonzales, F., Mangelsdorf, D.J., Wang, M.Y., Richardson, C., Witters, L.A., Unger, R.H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  24. 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]
  25. PPARalpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice. Tanaka, N., Moriya, K., Kiyosawa, K., Koike, K., Gonzalez, F.J., Aoyama, T. J. Clin. Invest. (2008) [Pubmed]
  26. Glucose directly links to lipid metabolism through high affinity interaction with peroxisome proliferator-activated receptor alpha. Hostetler, H.A., Huang, H., Kier, A.B., Schroeder, F. J. Biol. Chem. (2008) [Pubmed]
  27. Metabolomics of the interaction between PPAR-alpha and age in the PPAR-alpha-null mouse. Atherton, H.J., Gulston, M.K., Bailey, N.J., Cheng, K.K., Zhang, W., Clarke, K., Griffin, J.L. Mol. Syst. Biol. (2009) [Pubmed]
  28. Identification of a functional peroxisome proliferator-responsive element in the murine fatty acid transport protein gene. Frohnert, B.I., Hui, T.Y., Bernlohr, D.A. J. Biol. Chem. (1999) [Pubmed]
  29. Responses of insulin-like growth factor (IGF)-I and IGF-binding proteins to nutritional status in peroxisome proliferator-activated receptor-alpha knockout mice. Lewitt, M.S., Brismar, K., Wang, J., Wivall-Helleryd, I.L., Sindelar, P., Gonzalez, F.J., Bergman, T., Bobek, G.A. Growth Horm. IGF Res. (2001) [Pubmed]
  30. Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. II. LXRs suppress lipid degradation gene promoters through inhibition of PPAR signaling. Ide, T., Shimano, H., Yoshikawa, T., Yahagi, N., Amemiya-Kudo, M., Matsuzaka, T., Nakakuki, M., Yatoh, S., Iizuka, Y., Tomita, S., Ohashi, K., Takahashi, A., Sone, H., Gotoda, T., Osuga, J., Ishibashi, S., Yamada, N. Mol. Endocrinol. (2003) [Pubmed]
  31. 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]
  32. Uncoupling protein 3 transcription is regulated by peroxisome proliferator-activated receptor (alpha) in the adult rodent heart. Young, M.E., Patil, S., Ying, J., Depre, C., Ahuja, H.S., Shipley, G.L., Stepkowski, S.M., Davies, P.J., Taegtmeyer, H. FASEB J. (2001) [Pubmed]
  33. Activation of peroxisome proliferator-activated receptor alpha increases the expression and activity of microsomal triglyceride transfer protein in the liver. Améen, C., Edvardsson, U., Ljungberg, A., Asp, L., Akerblad, P., Tuneld, A., Olofsson, S.O., Lindén, D., Oscarsson, J. J. Biol. Chem. (2005) [Pubmed]
  34. Absence of spontaneous peroxisome proliferation in enoyl-CoA Hydratase/L-3-hydroxyacyl-CoA dehydrogenase-deficient mouse liver. Further support for the role of fatty acyl CoA oxidase in PPARalpha ligand metabolism. Qi, C., Zhu, Y., Pan, J., Usuda, N., Maeda, N., Yeldandi, A.V., Rao, M.S., Hashimoto, T., Reddy, J.K. J. Biol. Chem. (1999) [Pubmed]
  35. 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]
  36. 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]
  37. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Sekiya, M., Yahagi, N., Matsuzaka, T., Najima, Y., Nakakuki, M., Nagai, R., Ishibashi, S., Osuga, J., Yamada, N., Shimano, H. Hepatology (2003) [Pubmed]
  38. 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]
  39. Peroxisome proliferators compete and ameliorate Hcy-mediated endocardial endothelial cell activation. Hunt, M.J., Tyagi, S.C. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  40. Impaired Ras membrane association and activation in PPARalpha knockout mice after partial hepatectomy. Wheeler, M.D., Smutney, O.M., Check, J.F., Rusyn, I., Schulte-Hermann, R., Thurman, R.G. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  41. Identification of novel peroxisome proliferator-activated receptor alpha (PPARalpha) target genes in mouse liver using cDNA microarray analysis. Cherkaoui-Malki, M., Meyer, K., Cao, W.Q., Latruffe, N., Yeldandi, A.V., Rao, M.S., Bradfield, C.A., Reddy, J.K. Gene Expr. (2001) [Pubmed]
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