PGC1α expression is controlled in skeletal muscles by PPARβ, whose ablation results in fiber-type switching, obesity, and type 2 diabetes
PGC1α expression is controlled in skeletal muscles by PPARβ, whose ablation results in fiber-type switching, obesity, and type 2 diabetes
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DOI：
10.1016/j.cmet.2006.10.003
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发表时间：
2006-11-01
期刊：
影响因子：
29
通讯作者：
Metzger, Daniel
中科院分区：
文献类型：
--
作者：
Schuler, Michael;Ali, Faisal;Metzger, Daniel
在骨骼肌肌细胞中选择性消融过氧化物酶体增殖物激活受体β（PPAR β）的小鼠被产生，以阐明这些肌细胞中PPAR β信号传导所起的作用。这些体细胞突变小鼠在肥胖和糖尿病发生之前表现出向较低氧化能力的肌纤维类型转换，从而证明了PPAR β在肌细胞中有助于维持氧化纤维，并且纤维类型转换可能是这些代谢紊乱的原因而不是后果。我们还表明，过氧化物酶体增殖物激活受体β刺激在肌细胞中的PGC 1 α，各种转录因子的共激活因子，已知在缓慢的肌纤维形成中发挥重要作用的表达。此外，由于PGC 1 α启动子含有PPAR应答元件，因此PPAR β对慢肌纤维形成和/或维持的作用可至少部分归因于在转录水平上刺激PGC 1 α表达。
Mice in which peroxisome proliferator-activated receptor beta (PPAR beta) is selectively ablated in skeletal muscle myocytes were generated to elucidate the role played by PPAR beta signaling in these myocytes. These somatic mutant mice exhibited a muscle fiber-type switching toward lower oxidative capacity that preceded the development of obesity and diabetes, thus demonstrating that PPAR beta is instrumental in myocytes to the maintenance of oxidative fibers and that f iber-type switching is likely to be the cause and not the consequence of these metabolic disorders. We also show that PPAR beta stimulates in myocytes the expression of PGC1 alpha, a coactivator of various transcription factors, known to play an important role in slow muscle fiber formation. Moreover, as the PGC1 alpha promoter contains a PPAR response element, the effect of PPAR beta on the formation and/or maintenance of slow muscle fibers can be ascribed, at least in part, to a stimulation of PGC1 alpha expression at the transcriptional level.