Muscle-selective knockout of AMPKα2 does not exacerbate diet-induced obesity probably related to altered myokines expression.

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.