Exercise training attenuates the hypermuscular phenotype and restores skeletal muscle function in the myostatin null mouse

Matsakas, Antonios; Macharia, Raymond; Otto, Anthony; Elashry, Mohamed I.; Mouisel, Etienne; Romanello, Vanina; Sartori, Roberta; Amthor, Helge; Sandri, Marco; Narkar, Vihang; Patel, Ketan

Abstract

Myostatin regulates both muscle mass and muscle metabolism. The myostatin null (MSTN -/- ) mouse has a hypermuscular phenotype owing to both hypertrophy and hyperplasia of the myofibres. The enlarged muscles display a reliance on glycolysis for energy production; however, enlarged muscles that develop in the absence of myostatin have compromised force-generating capacity. Recent evidence has suggested that endurance exercise training increases the oxidative properties of muscle. Here, we aimed to identify key changes in the muscle phenotype of MSTN -/- mice that can be induced by training. To this end, we subjected MSTN -/- mice to two different forms of training, namely voluntary wheel running and swimming, and compared the response at the morphological, myocellular and molecular levels. We found that both regimes normalized changes of myostatin deficiency and restored muscle function. We showed that both exercise training regimes increased muscle capillary density and the expression of Ucp3, Cpt1α, Pdk4 and Errγ, key markers for oxidative metabolism. Cross-sectional area of hypertrophic myofibres from MSTN -/- mice decreased towards wild-type values in response to exercise and, in this context, Bnip3, a key autophagy-related gene, was upregulated. This reduction in myofibre size caused an increase of the nuclear-to-cytoplasmic ratio towards wild-type values. Importantly, both training regimes increased muscle force in MSTN -/- mice. We conclude that impaired skeletal muscle function in myostatin-deficient mice can be improved through endurance exercise-mediated remodelling of muscle fibre size and metabolic profile. © 2011 The Authors. Experimental Physiology © 2012 The Physiological Society.

Citation

Matsakas, A., Macharia, R., Otto, A., Elashry, M. I., Mouisel, E., Romanello, V., …Patel, K. (2012). Exercise training attenuates the hypermuscular phenotype and restores skeletal muscle function in the myostatin null mouse. Experimental Physiology, 97(1), 125-140. https://doi.org/10.1113/expphysiol.2011.063008

• Journal Article Type: Article
• Acceptance Date: Nov 4, 2011
• Online Publication Date: Dec 8, 2011
• Publication Date: 2012-01
• Deposit Date: Nov 13, 2014
• Journal: Experimental Physiology
• Print ISSN: 1469-445X
• Electronic ISSN: 1469-445X
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 97
• Issue: 1
• Pages: 125-140
• DOI: https://doi.org/10.1113/expphysiol.2011.063008
• Keywords: Physiology
• Public URL: https://hull-repository.worktribe.com/output/469476
• Publisher URL: https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/expphysiol.2011.063008