A role for the transcriptional coactivator PGC-1alpha in muscle refueling.
A role for the transcriptional coactivator PGC-1alpha in muscle refueling.
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发表时间：
2007
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通讯作者：
A. Wende;P. Schaeffer;G. Parker;C. Zechner;Dong‐Ho Han;May M. Chen;C. Hancock;J. J. Lehman-J.
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作者：
A. Wende;P. Schaeffer;G. Parker;C. Zechner;Dong‐Ho Han;May M. Chen;C. Hancock;J. J. Lehman-J.
转录辅激活因子过氧化物酶体增殖物激活受体γ辅激活因子-1 α（PGC-1 α）已被鉴定为线粒体功能的诱导型调节因子。运动后诱导骨骼肌PGC-1 α表达。因此，我们试图确定其在调节肌肉燃料代谢中的作用。使用条件性、肌肉特异性、PGC-1 α功能获得性和组成性、全身性、功能丧失性小鼠进行研究。PGC-1 α的强制表达增加了肌肉葡萄糖摄取，同时增加了糖原储存，这是一种类似于运动后恢复的代谢反应。肌肉PGC-1 α表达的诱导防止了运动过程中的肌糖原消耗。相反，PGC-1 α缺乏的动物表现出运动后肌糖原补充率降低。PGC-1 α被证明通过几种机制增加肌糖原储存，包括刺激葡萄糖输入，抑制糖酵解通量，以及下调糖原磷酸化酶及其活化激酶磷酸化酶激酶α的表达。这些发现将PGC-1 α确定为骨骼肌燃料储存的关键调节剂。
The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) has been identified as an inducible regulator of mitochondrial function. Skeletal muscle PGC-1alpha expression is induced post-exercise. Therefore, we sought to determine its role in the regulation of muscle fuel metabolism. Studies were performed using conditional, muscle-specific, PGC-1alpha gain-of-function and constitutive, generalized, loss-of-function mice. Forced expression of PGC-1alpha increased muscle glucose uptake concomitant with augmentation of glycogen stores, a metabolic response similar to post-exercise recovery. Induction of muscle PGC-1alpha expression prevented muscle glycogen depletion during exercise. Conversely, PGC-1alpha-deficient animals exhibited reduced rates of muscle glycogen repletion post-exercise. PGC-1alpha was shown to increase muscle glycogen stores via several mechanisms including stimulation of glucose import, suppression of glycolytic flux, and by down-regulation of the expression of glycogen phosphorylase and its activating kinase, phosphorylase kinase alpha. These findings identify PGC-1alpha as a critical regulator of skeletal muscle fuel stores.