Brun R P, Tontonoz P, Forman B M, Ellis R, Chen J, Evans R M, Spiegelman B M
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes Dev. 1996 Apr 15;10(8):974-84. doi: 10.1101/gad.10.8.974.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor expressed predominantly in adipose tissue, where it plays a central role in the control of adipocyte gene expression and differentiation. Because there are two additional PPAR isoforms, PPARalpha and PPARdelta, and these are also expressed at some level in certain adipose depots, we have compared directly the adipogenic potential of all three receptors. Ectopically expressed PPARgamma powerfully induces adipogenesis at a morphological and molecular level in response to a number of PPARgamma activators. PPARalpha is less adipogenic but is able to induce significant differentiation in response to strong PPARalpha activators. Expression and activation of PPARdelta did not stimulate adipogenesis. Of the three PPARs, only PPARgamma can cooperate with C/EBPalpha in the promotion of adipogenesis. To begin to investigate the functional basis for the differential adipogenic activity of the PPAR isoforms, we have examined their ability to bind to several PPAR DNA response sequences. Compared with PPARalpha and PPARdelta, PPARgamma shows preferential binding to two well-characterized regulatory sequences derived from a fat-specific gene, ARE6 and ARE7. These data strongly suggest that PPARgamma is the predominant receptor regulating adipogenesis; however, they also suggest that PPARalpha may play a role in differentiation of certain adipose depots in response to a different set of physiologic activators or in certain disease states.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种主要在脂肪组织中表达的核激素受体，它在控制脂肪细胞基因表达和分化中起核心作用。由于还有另外两种PPAR亚型，即PPARα和PPARδ，且它们在某些脂肪储存部位也有一定程度的表达，我们直接比较了这三种受体的脂肪生成潜能。异位表达的PPARγ在多种PPARγ激活剂的作用下，能在形态和分子水平上强力诱导脂肪生成。PPARα的脂肪生成能力较弱，但在强PPARα激活剂的作用下能够诱导显著的分化。PPARδ的表达和激活并未刺激脂肪生成。在这三种PPAR中，只有PPARγ能与C/EBPα协同促进脂肪生成。为了开始研究PPAR亚型脂肪生成活性差异的功能基础，我们检测了它们与几种PPAR DNA反应序列结合的能力。与PPARα和PPARδ相比，PPARγ对源自脂肪特异性基因的两个特征明确的调控序列ARE6和ARE7表现出优先结合。这些数据强烈表明PPARγ是调节脂肪生成的主要受体；然而，它们也表明PPARα可能在某些脂肪储存部位对不同生理激活剂的反应或某些疾病状态下的分化中发挥作用。
