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Gene Review

Ppard  -  peroxisome proliferator activator receptor...

Mus musculus

Synonyms: NUC-1, NUC1, Nr1c2, Nuclear hormone receptor 1, Nuclear receptor subfamily 1 group C member 2, ...
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Disease relevance of Ppard


High impact information on Ppard

  • As predicted, acute treatment of Lepr(db/db) mice with a PPARdelta agonist depletes lipid accumulation [1].
  • In contrast to the well-established roles of PPARgamma and PPARalpha in lipid metabolism, little is known for PPARdelta in this process [1].
  • In vitro, activation of PPARdelta in adipocytes and skeletal muscle cells promotes fatty acid oxidation and utilization [1].
  • We show here that targeted activation of PPARdelta in adipose tissue specifically induces expression of genes required for fatty acid oxidation and energy dissipation, which in turn leads to improved lipid profiles and reduced adiposity [1].
  • In both the Min mutant and chemically induced mouse models, colon polyp formation was significantly greater in mice nullizygous for PPAR-delta [2].

Chemical compound and disease context of Ppard


Biological context of Ppard


Anatomical context of Ppard


Associations of Ppard with chemical compounds


Physical interactions of Ppard

  • This TGF-beta1/Smad3 action involves an inhibitory effect on AP-1 activity and DNA binding that results in an inhibition of the AP-1-driven induction of the PPARbeta/delta promoter [17].

Regulatory relationships of Ppard

  • Our data suggest that PPARdelta is not directly regulated by beta-catenin, and that inhibition of PPARdelta activity is unlikely to be an appropriate strategy for the chemoprevention or chemotherapy of intestinal malignancies [18].
  • Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expression [17].
  • In 3T3-L1 preadipocytes, simultaneous administration of a PPARdelta-selective ligand and MIX significantly enhanced the early expression of PPARgamma and ALBP/aP2, but only modestly promoted terminal differentiation as determined by lipid accumulation [19].
  • The results reveal a dual role of TGF-beta1 as a chemoattractant of inflammatory cells and repressor of inflammation-induced PPARbeta/delta expression [20].
  • Conversely, exposure of Rcho-1 cells to a PPARbeta/delta agonist triggers a massive differentiation via increased expression of 3-phosphoinositide-dependent kinase 1 and integrin-linked kinase and subsequent phosphorylation of Akt [21].
  • Myocardial injury due to ischemia/reperfusion injury was significantly reduced in the MHC-PPARbeta/delta mice compared with control or MHC-PPARalpha mice, consistent with an increased capacity for myocardial glucose utilization [22].

Other interactions of Ppard


Analytical, diagnostic and therapeutic context of Ppard


  1. 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]
  2. Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis. Harman, F.S., Nicol, C.J., Marin, H.E., Ward, J.M., Gonzalez, F.J., Peters, J.M. Nat. Med. (2004) [Pubmed]
  3. Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure. Letavernier, E., Perez, J., Joye, E., Bellocq, A., Fouqueray, B., Haymann, J.P., Heudes, D., Wahli, W., Desvergne, B., Baud, L. J. Am. Soc. Nephrol. (2005) [Pubmed]
  4. The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. Dressel, U., Allen, T.L., Pippal, J.B., Rohde, P.R., Lau, P., Muscat, G.E. Mol. Endocrinol. (2003) [Pubmed]
  5. Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta. Wang, D., Wang, H., Shi, Q., Katkuri, S., Walhi, W., Desvergne, B., Das, S.K., Dey, S.K., DuBois, R.N. Cancer Cell (2004) [Pubmed]
  6. PPARdelta regulates glucose metabolism and insulin sensitivity. Lee, C.H., Olson, P., Hevener, A., Mehl, I., Chong, L.W., Olefsky, J.M., Gonzalez, F.J., Ham, J., Kang, H., Peters, J.M., Evans, R.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Cloning and function of rabbit peroxisome proliferator-activated receptor delta/beta in mature osteoclasts. Mano, H., Kimura, C., Fujisawa, Y., Kameda, T., Watanabe-Mano, M., Kaneko, H., Kaneda, T., Hakeda, Y., Kumegawa, M. J. Biol. Chem. (2000) [Pubmed]
  8. GW-501516 GlaxoSmithKline/Ligand. Pelton, P. Current opinion in investigational drugs (London, England : 2000) (2006) [Pubmed]
  9. Localization of mouse peroxisome proliferator-activated receptor delta (Ppard) on chromosome 17 near colipase (Clps). Cohen, R.D., Welch, C., Xia, Y., Lusis, A.J., Reue, K. Mamm. Genome (1996) [Pubmed]
  10. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome. Tanaka, T., Yamamoto, J., Iwasaki, S., Asaba, H., Hamura, H., Ikeda, Y., Watanabe, M., Magoori, K., Ioka, R.X., Tachibana, K., Watanabe, Y., Uchiyama, Y., Sumi, K., Iguchi, H., Ito, S., Doi, T., Hamakubo, T., Naito, M., Auwerx, J., Yanagisawa, M., Kodama, T., Sakai, J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  11. Peroxisome proliferator-activated receptor beta (delta)-dependent regulation of ubiquitin C expression contributes to attenuation of skin carcinogenesis. Kim, D.J., Akiyama, T.E., Harman, F.S., Burns, A.M., Shan, W., Ward, J.M., Kennett, M.J., Gonzalez, F.J., Peters, J.M. J. Biol. Chem. (2004) [Pubmed]
  12. Peroxisome proliferator-activated receptor-beta/delta inhibits epidermal cell proliferation by down-regulation of kinase activity. Kim, D.J., Murray, I.A., Burns, A.M., Gonzalez, F.J., Perdew, G.H., Peters, J.M. J. Biol. Chem. (2005) [Pubmed]
  13. 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]
  14. Developmental and Tissue-Specific Involvement of Peroxisome Proliferator-Activated Receptor-{alpha} in the Control of Mouse Uncoupling Protein-3 Gene Expression. Pedraza, N., Rosell, M., Villarroya, J., Iglesias, R., Gonzalez, F.J., Solanes, G., Villarroya, F. Endocrinology (2006) [Pubmed]
  15. Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer. Gupta, R.A., Tan, J., Krause, W.F., Geraci, M.W., Willson, T.M., Dey, S.K., DuBois, R.N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  16. Inhibition of chemically induced skin carcinogenesis by sulindac is independent of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). Kim, D.J., Prabhu, K.S., Gonzalez, F.J., Peters, J.M. Carcinogenesis (2006) [Pubmed]
  17. Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expression. Tan, N.S., Michalik, L., Di-Poï, N., Ng, C.Y., Mermod, N., Roberts, A.B., Desvergne, B., Wahli, W. EMBO J. (2004) [Pubmed]
  18. PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine. Reed, K.R., Sansom, O.J., Hayes, A.J., Gescher, A.J., Winton, D.J., Peters, J.M., Clarke, A.R. Oncogene (2004) [Pubmed]
  19. Peroxisome proliferator-activated receptor delta (PPARdelta )-mediated regulation of preadipocyte proliferation and gene expression is dependent on cAMP signaling. Hansen, J.B., Zhang, H., Rasmussen, T.H., Petersen, R.K., Flindt, E.N., Kristiansen, K. J. Biol. Chem. (2001) [Pubmed]
  20. Genetic- or transforming growth factor-beta 1-induced changes in epidermal peroxisome proliferator-activated receptor beta/delta expression dictate wound repair kinetics. Tan, N.S., Michalik, L., Desvergne, B., Wahli, W. J. Biol. Chem. (2005) [Pubmed]
  21. Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor beta/delta. Nadra, K., Anghel, S.I., Joye, E., Tan, N.S., Basu-Modak, S., Trono, D., Wahli, W., Desvergne, B. Mol. Cell. Biol. (2006) [Pubmed]
  22. Nuclear receptors PPARbeta/delta and PPARalpha direct distinct metabolic regulatory programs in the mouse heart. Burkart, E.M., Sambandam, N., Han, X., Gross, R.W., Courtois, M., Gierasch, C.M., Shoghi, K., Welch, M.J., Kelly, D.P. J. Clin. Invest. (2007) [Pubmed]
  23. 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]
  24. Inhibition of PPAR alpha/RXR alpha-mediated direct hyperplasia pathways during griseofulvin-induced hepatocarcinogenesis. Nagao, Y., French, B.A., Cai, Y., French, S.W., Wan, Y.J. J. Cell. Biochem. (1998) [Pubmed]
  25. Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) alpha knock-out mice. Evidence for compensatory regulation by PPAR delta. Muoio, D.M., MacLean, P.S., Lang, D.B., Li, S., Houmard, J.A., Way, J.M., Winegar, D.A., Corton, J.C., Dohm, G.L., Kraus, W.E. J. Biol. Chem. (2002) [Pubmed]
  26. Protective effects of a peroxisome proliferator-activated receptor-beta/delta agonist in experimental autoimmune encephalomyelitis. Polak, P.E., Kalinin, S., Dello Russo, C., Gavrilyuk, V., Sharp, A., Peters, J.M., Richardson, J., Willson, T.M., Weinberg, G., Feinstein, D.L. J. Neuroimmunol. (2005) [Pubmed]
  27. Activators of peroxisome proliferator-activated receptor-alpha partially inhibit mouse skin tumor promotion. Thuillier, P., Anchiraico, G.J., Nickel, K.P., Maldve, R.E., Gimenez-Conti, I., Muga, S.J., Liu, K.L., Fischer, S.M., Belury, M.A. Mol. Carcinog. (2000) [Pubmed]
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