A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis
A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis
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DOI：
10.1016/s0092-8674(00)81410-5
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发表时间：
1998-03-20
期刊：
影响因子：
64.5
通讯作者：
Spiegelman, BM
中科院分区：
文献类型：
--
作者：
Puigserver, P;Wu, ZD;Spiegelman, BM
适应性产热是能量稳态的重要组成部分，也是抵抗肥胖的代谢防御。我们从棕色脂肪cDNA文库中克隆了一个新的核受体转录辅激活因子PGC-1。PGC-I mRNA的表达显着升高后，可乐暴露的小鼠在棕色脂肪和骨骼肌，关键产热组织。PGC-1极大地增加解偶联蛋白（UCP-1）启动子上的PPAR γ和甲状腺激素受体的转录活性。PGC-1在白色脂肪细胞中的异位表达激活UCP-1和呼吸链关键线粒体酶的表达，并增加线粒体DNA的细胞含量。这些结果表明PGC-1在连接核受体与适应性产热的转录程序中起关键作用。
Adaptive thermogenesis is an important component of energy homeostasis and a metabolic defense against obesity. We have cloned a novel transcriptional coactivator of nuclear receptors, termed PGC-1, from a brown fat cDNA library. PGC-I mRNA expression is dramatically elevated upon cola exposure of mice in both brown fat and skeletal muscle, key thermogenic tissues. PGC-1 greatly increases the transcriptional activity of PPAR gamma and the thyroid hormone receptor on the uncoupling protein (UCP-1) promoter. Ectopic expression of PGC-1 in white adipose cells activates expression of UCP-1 and key mitochondrial enzymes of the respiratory chain, and increases the cellular content of mitochondrial DNA. These results indicate that PGC-1 plays a key role in linking nuclear receptors to the transcriptional program of adaptive thermogenesis.