Date of Graduation
School of Medicine
David L. Williamson.
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.
Drake, Joshua C., "Long term AMPK activation limits obesity induced muscle atrophy" (2010). Graduate Theses, Dissertations, and Problem Reports. 2992.