AMP-activated kinase α2 deficiency protects mice from denervation-induced skeletal muscle atrophy

AMP-activated protein kinase (AMPK) is a master regulator of skeletal muscle metabolic pathways. Recently, AMPK activation by AICAR has been shown to increase myofibrillar protein degradation in C2C12 myotubes via stimulating autophagy and ubiquitin proteasome system. However, the impact of AMPK alpha on denervation induced muscle atrophy has not been tested. In this study, we performed sciatic denervation on hind limb muscles in both wild type (WT) and AMPK alpha 2(-/-) mice. We found that AMPKa was phosphorylated in atrophic muscles following denervation. In addition, deletion of AMPK alpha 2 significantly attenuated denervation induced skeletal muscle wasting and protein degradation, as evidenced by preserved muscle mass and myofiber area, as well as lower levels of ubiquitinated protein, Atrogin-1 and MuRF-1 expression, and LC3-II/I ratio in tibial anterior (TA) muscles. Interestingly, the phosphorylated FoxO3a at Ser253 was significantly decreased in atrophic TA muscles, which was preserved in AMPK alpha 2(-/-) mice. Collectively, our data support the notion that the activation of AMPK alpha 2 contributes to the atrophic effects of denervation. (C) 2016 Elsevier Inc. All rights reserved.