Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China.
Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China.
J Nutr Biochem. 2018 Nov;61:155-162. doi: 10.1016/j.jnutbio.2018.08.007. Epub 2018 Sep 1.
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 I-SS, sirtuin1 (Sirt1) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) 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 Sirt1/AMPK pathway.
本研究探讨了精氨酸对小鼠骨骼肌纤维类型转变及 C2C12 肌管中的影响。我们的数据表明，饮食补充精氨酸可显著上调小鼠的慢肌肌球蛋白重链（MyHC）、肌钙蛋白 I-SS、沉默调节蛋白 1（Sirt1）和过氧化物酶体增殖物激活受体-γ共激活因子-1α（PGC-1α）蛋白表达，并显著下调快肌 MyHC 蛋白表达。在 C2C12 肌管中，精氨酸可显著增加慢肌 MyHC 蛋白水平和慢肌 MyHC 阳性细胞数量，同时显著降低快肌 MyHC 蛋白水平和快肌 MyHC 阳性细胞数量。我们还表明，精氨酸可增加小鼠和 C2C12 肌管中琥珀酸脱氢酶和苹果酸脱氢酶的活性，降低乳酸脱氢酶的活性。在此，我们发现精氨酸可激活小鼠和 C2C12 肌管中的 AMP 激活蛋白激酶（AMPK）。然而，用化合物 C 抑制 AMPK 活性可显著减弱精氨酸对 C2C12 肌管中慢肌 MyHC 和快肌 MyHC 表达的影响。最后，我们表明，用 EX527 抑制 Sirt1 表达可减弱精氨酸诱导的磷酸化-AMPK 和慢肌 MyHC 蛋白水平增加、一氧化氮合酶（NOS）mRNA 水平以及 NOS 和 NO 含量增加，以及快肌 MyHC 蛋白水平降低。综上，我们的研究结果表明，精氨酸通过 Sirt1/AMPK 通路促进骨骼肌纤维类型从快肌向慢肌转变。
