Nuclear receptor corepressor RIP140 regulates fat accumulation
Nuclear receptor corepressor RIP140 regulates fat accumulation
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DOI：
10.1073/pnas.0401013101
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发表时间：
2004-06-01
影响因子：
11.1
通讯作者：
Parker, MG
中科院分区：
文献类型：
--
作者：
Leonardsson, G;Steel, JH;Parker, MG
核受体及其共激活剂已被证明是脂肪组织生物学的关键调节因子。在这里，我们证明核受体的配体依赖性转录抑制因子在调节能量储存和能量消耗之间的平衡中发挥着至关重要的作用。缺乏辅阻遏蛋白 RIP140 的小鼠身材瘦削，对高脂饮食引起的肥胖和肝脂肪变性具有抵抗力，并且耗氧量增加。尽管脂肪生成过程不受影响，但某些脂肪生成酶的表达减少。相反，参与能量耗散和线粒体解偶联的基因，包括解偶联蛋白1，显着增加。因此，能量稳态的维持需要白色脂肪组织中转录抑制因子的作用，并且RIP140向核受体的配体依赖性募集可能为肥胖和相关疾病的治疗提供治疗靶点。
Nuclear receptors and their coactivators have been shown to function as key regulators of adipose tissue biology. Here we show that a ligand-dependent transcriptional repressor for nuclear receptors plays a crucial role in regulating the balance between energy storage and energy expenditure. Mice devoid of the corepressor protein RIP140 are lean, show resistance to high-fat diet-induced obesity and hepatic steatosis, and have increased oxygen consumption. Although the process of adipogenesis is unaffected, expression of certain lipogenic enzymes is reduced. In contrast, genes involved in energy dissipation and mitochondrial uncoupling, including uncoupling protein 1, are markedly increased. Therefore, the maintenance of energy homeostasis requires the action of a transcriptional repressor in white adipose tissue, and ligand-dependent recruitment of RIP140 to nuclear receptors may provide a therapeutic target in the treatment of obesity and related disorders.