Teruel T, Smith S A, Peterson J, Clapham J C
Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, NFSP-N, Third Avenue, Essex, Harlow, CM19 5AW, United Kingdom.
Biochem Biophys Res Commun. 2000 Jul 5;273(2):560-4. doi: 10.1006/bbrc.2000.2982.
Rat brown adipocytes express mRNAs for Uncoupling Proteins (UCP) 1, 2 and 3 and the Peroxisome Proliferator Activated Receptors (PPAR) alpha and gamma. We have examined the effects of selective PPARalpha or -gamma activation on changes in UCP-1 and UCP-3 mRNA levels in cultured fetal rat brown adipocytes (FBA). Rosiglitazone (1.0 microM), a selective PPARgamma agonist, elicited 5- and 3-fold increases in UCP-1 and UCP-3, respectively. The PPARalpha ligand, Wy14643 (10.0 microM) increased UCP-3 tenfold, but decreased UCP-1. A synergistic effect on UCP-3 expression (30-fold increase; P < 0. 05) was observed when FBA were exposed to a combination of Wy14643 (10.0 microM) and rosiglitazone (10.0 microM). Thus, activation of PPARgamma increases UCP-1 and UCP-3 levels which are differentially regulated by PPARalpha. A synergistic interaction occurs between PPARalpha and PPARgamma in the regulation of UCP-3 in FBA, probably via co-activator recruitment, suppression of co-repressor proteins or through a direct interaction at the level of the PPRE.
大鼠棕色脂肪细胞表达解偶联蛋白（UCP）1、2和3以及过氧化物酶体增殖物激活受体（PPAR）α和γ的信使核糖核酸。我们研究了选择性激活PPARα或γ对培养的胎鼠棕色脂肪细胞（FBA）中UCP-1和UCP-3信使核糖核酸水平变化的影响。罗格列酮（1.0微摩尔），一种选择性PPARγ激动剂，分别使UCP-1和UCP-3增加了5倍和3倍。PPARα配体Wy14643（10.0微摩尔）使UCP-3增加了10倍，但使UCP-1减少。当FBA暴露于Wy14643（10.0微摩尔）和罗格列酮（10.0微摩尔）的组合时，观察到对UCP-3表达有协同作用（增加30倍；P<0.05）。因此，激活PPARγ会增加UCP-1和UCP-3水平，而它们受到PPARα的不同调节。在FBA中，PPARα和PPARγ在UCP-3的调节中发生协同相互作用，可能是通过共激活因子募集、共抑制蛋白的抑制或在PPRE水平的直接相互作用。
