Transcriptional Regulation of Fat Metabolism by PPARgamm

过氧化物酶体增殖激活受体- γ (pparγ)和- δ (pparδ)是脂肪代谢的主要调节因子。它们属于配体激活转录因子的核受体超家族。高选择性的pparγ和pparδ配体是治疗2型糖尿病和肥胖的有希望的药物或候选药物。然而，这些配体作为抗糖尿病和/或抗肥胖药物的分子机制在很大程度上仍不清楚。核受体生物学的三方性质表明，配体的生物学效应是由配体、核受体和配体结合的核受体在靶基因启动子上募集的辅因子（共激活因子或辅抑制因子）这三部分的组合协同作用决定的。为了了解配体激活的PPARgamma和PPARdelta转录调节脂肪代谢的分子机制，已经启动了三个使用蛋白质组学和基因组学方法的项目：

Peroxisome proliferator-activated receptor-gamma (PPARgamma) and -delta (PPARdelta) are major regulators of fat metabolism. They belong to the nuclear receptor super-family of ligand activated transcription factors. Highly selective PPARgamma and PPARdelta ligands are promising drugs or drug candidates for the treatment of type 2 diabetes and obesity. However, the molecular mechanism by which these ligands act as anti-diabetes and/or anti-obesity agents has largely remained unclear. The tripartite nature of the nuclear receptor biology suggests that the biological effect of a ligand is determined by the combinatorial collaboration among these three parts: ligand, nuclear receptor, and cofactors (coactivators or corepressors) recruited by ligand-bound nuclear receptor on the target gene promoters. To understand the molecular mechanism by which ligand-activated PPARgamma and PPARdelta transcriptionally regulate fat metabolism, three projects using proteomic and genomic approaches have been initiated: I: Isolation and characterization of a histone methyltransferase complex that regulates PPARgamma transcriptional activity. II: Isolation and characterization of transcription cofactors for PPARdelta.