Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity.
Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity.
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DOI：
10.1016/j.cmet.2010.11.008
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发表时间：
2010-12-01
期刊：
影响因子：
29
通讯作者：
Kelly DP
中科院分区：
文献类型：
--
作者：
Zechner C;Lai L;Zechner JF;Geng T;Yan Z;Rumsey JW;Collia D;Chen Z;Wozniak DF;Leone TC;Kelly DP
有证据表明，PGC-1辅激活因子在骨骼肌代谢、功能和疾病中起关键作用。产生并表征骨骼肌中具有总PGC-1缺陷的小鼠（PGC-1α−/−βf/f/MLC-Cre小鼠）。与单一PGC-1α或PGC-1β缺陷小鼠和野生型对照相比，PGC-1 α−/−βf/f/MLC-Cre小鼠的运动表现显著降低。PGC-1α−/−βf/f/MLC-Cre小鼠的运动表型与肌肉呼吸能力的显著降低和线粒体结构紊乱（与融合/分裂和生物源性缺陷一致）以及运动期间肌肉糖原储备的快速消耗相关。令人惊讶的是，PGC-1α−/−βf/f/MLC-Cre小鼠的骨骼肌纤维类型与野生型小鼠没有显著差异。此外，胰岛素敏感性和葡萄糖耐量在PGC-1α−/−βf/f/MLC-Cre小鼠中没有改变。综上所述，我们得出结论，PGC-1辅激活剂是必要的骨骼肌的氧化和线粒体程序，但基本纤维类型的确定和胰岛素敏感性是不必要的。
Evidence is emerging that the PGC-1 coactivators serve a critical role in skeletal muscle metabolism, function, and disease. Mice with total PGC-1 deficiency in skeletal muscle (PGC-1α−/−βf/f/MLC-Cre mice) were generated and characterized. PGC-1α−/−βf/f/MLC-Cre mice exhibit a dramatic reduction in exercise performance compared to single PGC-1α- or PGC-1β-deficient mice and wild-type controls. The exercise phenotype of the PGC-1α−/−βf/f/MLC-Cre mice was associated with a marked diminution in muscle respiratory capacity and mitochondrial structural derangements consistent with fusion/fission and biogenic defects together with rapid depletion of muscle glycogen stores during exercise. Surprisingly, the skeletal muscle fiber type profile of the PGC-1α−/−βf/f/MLC-Cre mice was not significantly different than the wild-type mice. Moreover, insulin sensitivity and glucose tolerance were not altered in the PGC-1α−/−βf/f/MLC-Cre mice. Taken together, we conclude that PGC-1 coactivators are necessary for the oxidative and mitochondrial programs of skeletal muscle but are dispensable for fundamental fiber type determination and insulin sensitivity.
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