Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.
Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.
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DOI：
10.1371/journal.pone.0158055
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yamashita H
中科院分区：
文献类型：
--
作者：
Maruta H;Yoshimura Y;Araki A;Kimoto M;Takahashi Y;Yamashita H
此前，我们发现口服醋酸减少了大冢Long-Evans Tokushima肥胖大鼠肝脏中的脂肪生成，并抑制了脂肪组织中的脂肪积聚，这些肥胖大鼠表现为高血糖肥胖并伴有高胰岛素血症和胰岛素抵抗。醋酸组大鼠肝脏和骨骼肌细胞AMP活化蛋白激酶(AMPK)磷酸化水平升高，骨骼肌肌红蛋白和葡萄糖转运蛋白4(GLUT4)基因转录水平升高。提示，醋酸可改善骨骼肌脂代谢。在本研究中，我们检测了冰醋酸对骨骼肌细胞AMPK的激活以及对GLUT4和肌红蛋白表达的刺激，以阐明冰醋酸在骨骼肌细胞中的生理功能。加入培养液中的冰醋酸被L6细胞迅速摄取，经冰醋酸处理后AMPK被磷酸化。我们观察到GLUT4和肌红蛋白的基因和蛋白表达增加。与未处理的细胞相比，L6细胞对葡萄糖和脂肪酸的摄取增加，而甘油三酯的积累较低。此外，处理细胞还表现出肌细胞增强因子2A(MEF2A)的基因和蛋白表达增加，这是一种众所周知的转录因子，参与肌红蛋白和GLUT4基因的表达。这些结果表明，醋酸通过激活AMPK促进葡萄糖摄取和脂肪酸代谢，并增加GLUT4和肌红蛋白的表达。
Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.