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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >PPARγ coactivator 1β/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity
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PPARγ coactivator 1β/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity

机译：PPARγ共激活因子1β/ ERR配体1是ERR蛋白配体，其表达诱导高能量消耗并拮抗肥胖

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摘要

A well balanced body energy budget controlled by limitation of calorie uptake and/or increment of energy expenditure, which is typically achieved by proper physical exercise, is most effective against obesity and diabetes mellitus. Recently, peroxisome proliferator-activated receptor (PPAR) γ, a member of the nuclear receptor, and its cofactors have been shown to be involved in lipid metabolism and in the control of energy expenditure. Here we show that PPARγ coactivator 1 (PGC-1) β functions as ERRL1 (for ERR ligand 1), which can bind and activate orphan ERRs (estrogen receptor-related receptors) in vitro. Consistently, PGC-1β/ERRL1 transgenic mice exhibit increased expression of the medium-chain acyl CoA dehydrogenase, a known ERR target and a pivotal enzyme of mitochondrial β-oxida-tion in skeletal muscle. As a result, the PGC-1β/ERRL1 mice show a state similar to an athlete; namely, the mice are hyperphagic and of elevated energy expenditure and are resistant to obesity induced by a high-fat diet or by a genetic abnormality. These results demonstrate that PGC-1β/ERRL1 can function as a protein ligand of ERR, and that its level contributes to the control of energy balance in vivo, and provide a strategy for developing novel antiobesity drugs.
机译：通常通过适当的体育锻炼，通过限制卡路里摄取和/或增加能量消耗来控制的均衡身体能量预算，最有效地对抗肥胖症和糖尿病。近来，已经证明过氧化物酶体增殖物激活受体（PPAR）γ是核受体的成员，其辅因子参与脂质代谢和能量消耗的控制。在这里，我们显示PPARγ共激活因子1（PGC-1）β发挥ERRL1（对于ERR配体1）的作用，它可以在体外结合并激活孤立的ERRs（与雌激素受体相关的受体）。一致地，PGC-1β/ ERRL1转基因小鼠在骨骼肌中表现出中链酰基辅酶A脱氢酶，已知的ERR标靶和线粒体β-氧化作用的关键酶表达增加。结果，PGC-1β/ ERRL1小鼠表现出与运动员相似的状态。就是说，小鼠是食欲亢进的并且能量消耗增加，并且对高脂饮食或遗传异常引起的肥胖具有抵抗力。这些结果表明PGC-1β/ ERRL1可以作为ERR的蛋白质配体，并且其水平有助于体内能量平衡的控制，并为开发新型抗肥胖药提供了策略。

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