Overexpression of peroxisome proliferator-activated receptor γ coactivator-1α down-regulates GLUT4 mRNA in skeletal muscles
Overexpression of peroxisome proliferator-activated receptor γ coactivator-1α down-regulates GLUT4 mRNA in skeletal muscles
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DOI：
10.1074/jbc.m304312200
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发表时间：
2003-08-15
影响因子：
4.8
通讯作者：
Ezaki, O
中科院分区：
文献类型：
--
作者：
Miura, S;Kai, Y;Ezaki, O
运动训练会增加骨骼肌中的线粒体和 GLUT4。最近的研究表明，通过运动增加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 1α (PGC-1α) 的表达可能会促进线粒体生物发生和脂肪酸氧化。为了检查 PGC-1α 表达的增加是否也导致 GLUT4 表达的增加，制备了在由人 α-骨骼肌动蛋白启动子驱动的骨骼肌中过度表达 PGC-1α 的转基因小鼠。 PGC-1α 在骨骼肌中过度表达，包括 I 型和 II 型富含纤维的肌肉，但在心脏中则不然。随着PGC-1α mRNA的增加，富含II型纤维的肌肉变得更红，骨骼肌中线粒体氧化代谢基因上调，而GLUT4 mRNA的表达意外下调。在 GLUT4 mRNA 减少的同时，观察到腹膜内注射胰岛素后血糖控制受损。因此，PGC-1α 的增加在增加线粒体生物合成和脂肪酸氧化方面发挥作用，但在增加骨骼肌中的 GLUT4 mRNA 方面没有作用。
Exercise training increases mitochondria and GLUT4 in skeletal muscles. Recent studies indicate that an increased expression of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) by exercise may promote mitochondrial biogenesis and fatty acid oxidation. To examine whether increased PGC-1alpha expression was also responsible for an increase of GLUT4 expression, transgenic mice that overexpress PGC-1alpha in skeletal muscles driven by a human alpha-skeletal actin promoter were made. PGC-1alpha was overexpresssed in skeletal muscles including type I and II fiber-rich muscles but not in the heart. With an increase of PGC-1alpha mRNA, type II fiber-rich muscles were redder, and genes of mitochondrial oxidative metabolism were up-regulated in skeletal muscles, whereas the expression of GLUT4 mRNA was unexpectedly downregulated. In parallel with a decrease of GLUT4 mRNA, an impairment of glycemic control after intraperitoneal insulin administration was observed. Thus, an increase of PGC-1alpha plays a role in increasing mitochondrial biogenesis and fatty acid oxidation but not in increasing GLUT4 mRNA in skeletal muscles.