Arginine promotes skeletal muscle fiber type transformation from fast-twitch to slow-twitch via Sirt1/AMPK pathway
Arginine promotes skeletal muscle fiber type transformation from fast-twitch to slow-twitch via Sirt1/AMPK pathway
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DOI：
10.1016/j.jnutbio.2018.08.007
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发表时间：
2018-11-01
影响因子：
5.6
通讯作者：
Huang, Zhiqing
中科院分区：
文献类型：
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作者：
Chen, Xiaoling;Guo, Yafei;Huang, Zhiqing
本研究探讨了精氨酸对小鼠和C2 C12肌管中骨骼肌纤维类型转化的影响。我们的数据显示，在小鼠的饮食中补充精氨酸显著上调慢肌球蛋白重链（MyHC）、肌钙蛋白1-SS、去乙酰化酶1（Sirtl）和过氧化物酶体增殖物激活受体-γ共激活因子-1 α（PGC-1 α）蛋白的表达，并且显著下调快肌球蛋白重链（MyHC）蛋白的表达。在C2 C12肌管中，精氨酸显著增加慢MyHC的蛋白水平和慢MyHC阳性细胞的数量，以及显著降低快MyHC的蛋白水平和快MyHC阳性细胞的数量。我们还表明，精氨酸增加琥珀酸脱氢酶和苹果酸脱氢酶的活性，降低小鼠和C2 C12肌管中的乳酸脱氢酶的活性。在这里，我们发现，在小鼠和C2 C12肌管中，AMP激活的蛋白激酶（AMPK）被精氨酸激活。然而，化合物C对AMPK活性的抑制显著减弱了精氨酸对C2 C12肌管中慢MyHC和快MyHC表达的影响。最后，我们发现，通过EX 527抑制Sirt 1表达减弱了甘氨酸诱导的磷酸化AMPK和慢MyHC蛋白水平、一氧化氮合酶（NOS）mRNA水平以及NOS和NO含量的增加，以及快MyHC蛋白水平的降低。总之，我们的研究结果表明，精氨酸通过Sirt 1/AMPK途径促进骨骼肌纤维类型从快收缩转换为慢收缩。(C)2018爱思唯尔公司All rights reserved.
This study investigated the effect of arginine on skeletal muscle fiber type transformation in mice and in C2C12 myotubes. Our data showed that dietary supplementation of arginine in mice significantly up-regulated the slow myosin heavy chain (MyHC), troponin 1-SS, sirtuinl (Sirtl) and peroxisome proliferator activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) protein expressions, as well as significantly down-regulated the fast MyHC protein expression. In C2C12 myotubes, arginine significantly increased the protein level of slow MyHC and the number of slow MyHC-positive cells, as well as significantly decreased the protein level of fast MyHC and the number of fast MyHC-positive cells. We also showed that arginine increased the activities of succinic dehydrogenase and malate dehydrogenase and decreased the activity of lactate dehydrogenase in mice and in C2C12 myotubes. Here we found that AMP-activated protein kinase (AMPK) was activated by arginine in mice and in C2C12 myotubes. However, inhibition of AMPK activity by compound C significantly attenuated the effects of arginine on slow MyHC and fast MyHC expressions in C2C12 myotubes. Finally, we showed that inhibition of Sirt1 expression by EX527 attenuated arginine-induced increase in the protein levels of phospho-AMPK and slow MyHC, the mRNA level of nitric oxide synthase (NOS) and the contents of NOS and NO, as well as decrease in fast MyHC protein level. Together, our findings indicated that arginine promotes skeletal muscle fiber type switching from fast-twitch to slow twitch via Sirtl/AMPK pathway. (C) 2018 Elsevier Inc. All rights reserved.