Leucine regulates slow-twitch muscle fibers expression and mitochondrial function by Sirt1/AMPK signaling in porcine skeletal muscle satellite cells
Leucine regulates slow-twitch muscle fibers expression and mitochondrial function by Sirt1/AMPK signaling in porcine skeletal muscle satellite cells
复制标题
亮氨酸通过 Sirt1/AMPK 信号在猪骨骼肌卫星细胞中调节慢肌纤维表达和线粒体功能
DOI：
10.1111/asj.13146
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发表时间：
2019-02-01
影响因子：
2
通讯作者：
Huang, Zhiqing
中科院分区：
文献类型：
--
作者：
Chen, Xiaoling;Xiang, Lu;Huang, Zhiqing
先前的研究表明，亮氨酸上调C2 C12细胞中慢肌球蛋白重链mRNA的表达。然而，亮氨酸在猪骨骼肌卫星细胞慢肌纤维表达和线粒体功能中的作用及其机制尚不清楚。在这项研究中，猪骨骼肌卫星细胞培养在分化培养基中处理与2 mM亮氨酸3天。使用Sirt 1抑制剂EX 527、AMPK抑制剂化合物C和AMPK α 1 siRNA来检查其潜在机制。在这里，我们发现，亮氨酸增加慢收缩肌纤维和线粒体功能相关的基因表达，以及增加琥珀酸脱氢酶（SDH）和苹果酸脱氢酶（MDH）的活动。此外，亮氨酸增加了Sirt 1和磷酸化AMPK的蛋白水平。我们还发现AMPK α 1 siRNA、AMPK抑制剂化合物C或Sirt 1抑制剂EX 527减弱了亮氨酸对慢收缩肌纤维和线粒体功能相关基因表达的积极作用。最后，我们发现Sirt 1是亮氨酸诱导的AMPK激活所必需的。我们的研究结果首次证明亮氨酸通过Sirt 1/AMPK信号通路诱导猪骨骼肌卫星细胞慢收缩肌纤维表达并改善线粒体功能。
A previous study demonstrated that leucine upregulates the slow myosin heavy chain mRNA expression in C2C12 cells. However, the role of leucine in slow-twitch muscle fibers expression and mitochondrial function of porcine skeletal muscle satellite cells as well as its mechanism remain unclear. In this study, porcine skeletal muscle satellite cells cultured in differentiation medium were treated with 2 mM leucine for 3 days. Sirt1 inhibitor EX527, AMPK inhibitor compound C, and AMPK alpha 1 siRNA were used to examine its underlying mechanism. Here we showed that leucine increased slow-twitch muscle fibers and mitochondrial function-related gene expression, as well as increased succinic dehydrogenase (SDH) and malate dehydrogenase (MDH) activities. Moreover, leucine increased the protein levels of Sirt1 and phospho-AMPK. We also found that AMPK alpha 1 siRNA, AMPK inhibitor compound C, or Sirt1 inhibitor EX527 attenuated the positive effect of leucine on slow-twitch muscle fibers and mitochondrial function-related gene expression. Finally, we showed that Sirt1 was required for leucine-induced AMPK activation. Our results provide, for the first time, evidence that leucine induces slow-twitch muscle fibers expression and improves mitochondrial function through Sirt1/AMPK signaling pathway in porcine skeletal muscle satellite cells.