Estrogen-related receptor gamma is a key regulator of muscle mitochondrial activity and oxidative capacity.
Estrogen-related receptor gamma is a key regulator of muscle mitochondrial activity and oxidative capacity.
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DOI：
10.1074/jbc.m110.125401
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发表时间：
2010-07-16
期刊：
影响因子：
--
通讯作者：
Markovits J
中科院分区：
文献类型：
--
作者：
Rangwala SM;Wang X;Calvo JA;Lindsley L;Zhang Y;Deyneko G;Beaulieu V;Gao J;Turner G;Markovits J
雌激素相关受体γ（ERRγ）调节围产期心肌氧化代谢的转换。我们想了解运动诱导骨骼肌ERRγ表达的意义。肌肉特异性VP 16 ERR γ转基因小鼠表现出运动能力、线粒体酶活性和线粒体增大，尽管肌肉重量较低。此外，与对照同窝仔相比，转基因小鼠的峰值氧化能力更高。相反，缺乏一个ERRγ拷贝的小鼠表现出运动能力和肌肉线粒体功能下降。有趣的是，我们观察到肌肉中ERRγ的增加产生的基因表达谱与红色氧化纤维型肌肉的基因表达谱紧密重叠。我们进一步证明了ERRβ/γ的小分子激动剂可以增加小鼠肌管中的线粒体功能。我们的数据表明，ERRγ在引起向慢收缩肌类型的转变以及伴随的更大的耐力运动能力方面起着重要作用。因此，这种核受体的激活为诸如肥胖症的疾病的治疗干预提供了潜在的节点，肥胖症与骨骼肌中氧化代谢降低和I型纤维含量降低有关。
Estrogen-related receptor γ (ERRγ) regulates the perinatal switch to oxidative metabolism in the myocardium. We wanted to understand the significance of induction of ERRγ expression in skeletal muscle by exercise. Muscle-specific VP16ERRγ transgenic mice demonstrated an increase in exercise capacity, mitochondrial enzyme activity, and enlarged mitochondria despite lower muscle weights. Furthermore, peak oxidative capacity was higher in the transgenics as compared with control littermates. In contrast, mice lacking one copy of ERRγ exhibited decreased exercise capacity and muscle mitochondrial function. Interestingly, we observed that increased ERRγ in muscle generates a gene expression profile that closely overlays that of red oxidative fiber-type muscle. We further demonstrated that a small molecule agonist of ERRβ/γ can increase mitochondrial function in mouse myotubes. Our data indicate that ERRγ plays an important role in causing a shift toward slow twitch muscle type and, concomitantly, a greater capacity for endurance exercise. Thus, the activation of this nuclear receptor provides a potential node for therapeutic intervention for diseases such as obesity, which is associated with reduced oxidative metabolism and a lower type I fiber content in skeletal muscle.