Long term AMPK activation limits obesity induced muscle atrophy .

摘要

The aim of this study was to identify obesity-induced alterations in regulatory mechanisms of skeletal muscle mass and how they would be altered with long term (8 weeks) AMPK-agonist treatment. 8 week old male, lean (L) wild type [body weight (BW) = 26.9 g] and ob/ob (O) [BW = 46.2 g] mice were fed an AMP kinase (AMPK) activator, beta-GPA (F), mixed at a 1% concentration within their food or normal chow as control (C) for 8 weeks. Following an overnight (12 hr) fast, all mice were sacrificed and the gastrocnemius complex was excised for analysis. Muscle mass was lower in the OC mice (121.08 +/- 9.3 mg) versus LC (158.4 +/- 5.6 mg). This corresponded with decreases in raptor associated with mTOR. Following treatment, western analysis of OF muscle lysates displayed increased AMPK and acetyl-CoA carboxylase phosphorylation compared with LC and OC mice. OC mice displayed higher activation of mammalian Target of Rapamycin (mTOR)-regulated signaling (S6K1, 4E-BP1, and GSK3), which was reciprocally altered after 8 weeks of beta-GPA feeding. These data show that long term (8 week) AMPK-agonist treatment can augment obesity-induced alterations in regulatory mechanisms of skeletal muscle mass through the normalization to lean levels of mTOR signaling.