AMPK and ACC phosphorylation:: Effect of leptin, muscle fibre type and obesity

Leptin stimulates fatty acid oxidation via the phosphorylation of AMPK (AMP-activated protein kinase) and ACC (acetyl-CoA carboxylase). Obesity is associated with resistance to the effects of leptin. We determined the action of leptin on AMPK alpha and ACC beta phosphorylation and lipid metabolism in soleus (SOL) and extensor digitorum longus (EDL) muscles from lean and obese Wistar rats after 1 and 100nM leptin. Both leptin doses stimulated phosphorylation of AMPK alpha and ACC beta (P <= 0.05) only in EDL muscles from lean animals. Malonyl-CoA levels were decreased in EDL muscles from lean animals after 1 and 100 nM leptin and significantly after 100 nM leptin in obese animals (P <= 0.05). Long-chain fatty acyl-CoA concentrations were decreased in EDL muscles from both phenotypes after 100 nM leptin. AMPK activation by leptin occurred independently of energy-related metabolites. These data demonstrate that the leptin effect on AMPK alpha and ACC beta is muscle fibre type dependent and fails in diet-induced obesity. Crown Copyright (C) 2008 Published by Elsevier Ireland Ltd. All rights reserved.