AMPK Activation of Muscle Autophagy Prevents Fasting-Induced Hypoglycemia and Myopathy during Aging
Adam L Bujak, Justin D Crane, James S Lally, Rebecca J Ford, Sally J Kang, Irena A Rebalka, Alex E Green, Bruce E Kemp, Thomas J Hawke, Jonathan D Schertzer, Gregory R Steinberg
CELL METABOLISM | CELL PRESS | Published : 2015
The AMP-activated protein kinase (AMPK) activates autophagy, but its role in aging and fasting-induced muscle function has not been defined. Here we report that fasting mice lacking skeletal muscle AMPK (AMPK-MKO) results in hypoglycemia and hyperketosis. This is not due to defective fatty acid oxidation, but instead is related to a block in muscle proteolysis that leads to reduced circulating levels of alanine, an essential amino acid required for gluconeogenesis. Markers of muscle autophagy including phosphorylation of Ulk1 Ser555 and Ser757 and aggregation of RFP-LC3 puncta are impaired. Consistent with impaired autophagy, aged AMPK-MKO mice possess a significant myopathy characterized by..View full abstract
We thank Alba Guarne for the use of her laboratory equipment. This work was supported by grants and fellowships from the Natural Sciences and Engineering Research Council of Canada (G.R.S), the Australian National Health and Medical Research Council (B.E.K. and G.R.S.), and the Canadian Institutes of Health Research (G.R.S.) and supported in part by the Victorian Government's OIS Program (B.E.K.) and Canadian Foundation for Innovation (G.R.S. and T.J.H.). J.D.C. is supported by a MAC-Obesity postdoctoral fellowship. A.E.G. is supported by PhD scholarships from CIHR and MitoCanada. J.D.S is a Canadian Diabetes Association Scholar. G.R.S. is a Canada Research Chair in Metabolism and Obesity and the McMaster University J. Bruce Duncan Chair in Metabolic Diseases.