NCoR1 is a conserved physiological modulator of muscle mass and oxidative function.
NCoR1 is a conserved physiological modulator of muscle mass and oxidative function.
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NCOR1是肌肉质量和氧化功能的保守生理调节剂。
DOI：
10.1016/j.cell.2011.10.017
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发表时间：
2011-11-11
期刊：
影响因子：
64.5
通讯作者：
Auwerx J
中科院分区：
文献类型：
--
作者：
Yamamoto H;Williams EG;Mouchiroud L;Cantó C;Fan W;Downes M;Héligon C;Barish GD;Desvergne B;Evans RM;Schoonjans K;Auwerx J
转录辅调节因子控制许多转录因子的活性，并被认为对基因表达模式有广泛影响。我们在此表明，肌肉特异性核受体辅阻遏物1（NCoR1）基因敲除小鼠具有相当选择性的表型变化，其特征是由于肌肉质量以及线粒体数量和活性的增加而使运动耐力增强。控制肌肉功能的特定转录因子（如MEF2、PPARβ/δ和ERRs）的激活是这些表型改变的基础。在需要脂肪氧化重新设定转录程序以促进氧化代谢的条件下，NCoR1水平会降低。NCoR1调节氧化代谢的能力可能是保守的，因为秀丽隐杆线虫唯一的NCoR同源物gei - 8的敲低也显著增加了肌肉线粒体和呼吸作用。总之，我们的数据表明NCoR1在肌肉生理学中起适应性作用，并且干扰NCoR1的作用可用于改善肌肉功能。
Transcriptional coregulators control the activity of many transcription factors and are thought to have wide ranging effects on gene expression patterns. We show here that muscle-specific nuclear receptor corepressor 1 (NCoR1) knockout mice have rather selective phenotypic changes, characterized by enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARβ/δ and ERRs, underpinned these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation resetting transcriptional programs to boost oxidative metabolism. The capacity of NCoR1 to modulate oxidative metabolism may be conserved as the knockdown of gei-8, the sole C.elegans NCoR homolog, also robustly increased muscle mitochondria and respiration. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function.
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影响因子：
64.8
作者：
Alenghat, Theresa;Meyers, Katherine;Mullican, Shannon E.;Leitner, Kirstin;Adeniji-Adele, Adetoun;Avila, Jacqueline;Bucan, Maja;Ahima, Rexford S.;Kaestner, Klaus H.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
影响因子：
64.8
作者：
Hagberg, Carolina E.;Falkevall, Annelie;Eriksson, Ulf
通讯作者：
Eriksson, Ulf
影响因子：
64.8
作者：
Jepsen, Kristen;Solum, Derek;Rosenfeld, Michael G.
通讯作者：
Rosenfeld, Michael G.
影响因子：
2.5
作者：
Champy, Marie-France;Selloum, Mohammed;Auwerx, Johan
通讯作者：
Auwerx, Johan
DOI：
10.1126/science.1198125
发表时间：
2011-03-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Feng D;Liu T;Sun Z;Bugge A;Mullican SE;Alenghat T;Liu XS;Lazar MA
通讯作者：
Lazar MA