Chen Ting, Li Zhongwen, Zhang Yanyan, Feng Fu, Wang Xiaobin, Wang Xinxia, Shen Qingwu W
Department of Animal Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
College of Animal Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China.
Biochem Biophys Res Commun. 2015 Mar 13;458(3):449-455. doi: 10.1016/j.bbrc.2015.01.075. Epub 2015 Jan 28.
Dysregulation of lipid metabolism has been believed to be central in the development of skeletal muscle insulin resistance. Since first being described in 1989, the role of AMPK in energy metabolism, especially its role in lipid metabolism in skeletal muscle has been well studied. However, some recent literature report that fatty acid oxidation in skeletal muscle is not directly associated with AMPK activation and ACC phosphorylation. To further understand the role of AMPK in lipid metabolism and the development of induced obesity and insulin resistance, muscle specific AMPKα2 knockout mice (mAMPKα2-KO) was employed in this study. The results showed that AMPKα2 ablation in muscle did not exacerbate high fat diet induce obesity in mice. On the contrary, it improved animal glucose tolerance and insulin sensitivity, with reduced triglyceride content in skeletal muscle and fat mass in various adipose tissues, when mice were fed high fat diet for 14 weeks. Gene expression analysis revealed that AMPKα2 knockout up-regulated the expression of genes related to lipid catabolism and down-regulated that of genes related to triglyceride synthesis. More importantly, ablation of AMPKα2 altered the expression of several myokines related to adipogenesis and muscle regeneration. Our data suggest that defect in AMPKα2 signaling does not necessarily lead to the development of muscle insulin resistance and obesity. AMPKα2 may regulate whole body lipid metabolism by regulating myokine secretion.
脂质代谢失调被认为是骨骼肌胰岛素抵抗发展的核心因素。自1989年首次被描述以来，AMPK在能量代谢中的作用，尤其是其在骨骼肌脂质代谢中的作用，已得到充分研究。然而，最近一些文献报道，骨骼肌中的脂肪酸氧化与AMPK激活和ACC磷酸化并无直接关联。为了进一步了解AMPK在脂质代谢以及诱导肥胖和胰岛素抵抗发展中的作用，本研究采用了肌肉特异性AMPKα2基因敲除小鼠（mAMPKα2-KO）。结果显示，肌肉中AMPKα2基因敲除并未加剧高脂饮食诱导的小鼠肥胖。相反，当小鼠高脂饮食喂养14周时，它改善了动物的葡萄糖耐量和胰岛素敏感性，同时降低了骨骼肌中的甘油三酯含量以及各种脂肪组织中的脂肪量。基因表达分析表明，AMPKα2基因敲除上调了与脂质分解代谢相关基因的表达，下调了与甘油三酯合成相关基因的表达。更重要的是，AMPKα2基因敲除改变了几种与脂肪生成和肌肉再生相关的肌动蛋白的表达。我们的数据表明，AMPKα2信号缺陷不一定会导致肌肉胰岛素抵抗和肥胖的发展。AMPKα2可能通过调节肌动蛋白分泌来调节全身脂质代谢。
