We have shown that, despite their increased glycolytic muscle fiber composition, myostatin deficient mice are able to perform endurance exercise without incurring muscle damage. Myostatin deficient mice are able to successfully adapt to endurance exercise by increasing oxidative enzyme activity. Myostatin deficient mice do, however, have a decrease in overall exercise capacity. We have also analyzed gene expression changes in gastrocnemius skeletal muscle with and without myostatin inhibition in a model of diabetes to determine the molecular mechanisms of myostatin regulation of muscle metabolism at the molecular level. We have shown that myostatin inhibition specifically in muscle in a mouse model of lipodystrophy prevents the accumulation of triglycerides in muscle, the development of hyperglycemia, and hyperphagia. These results suggest that increased muscle may not only help prevent diabetes, but may also regulate food intake.

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Wang, Li; Jia, Yi; Rogers, Heather et al. (2013) Erythropoietin contributes to slow oxidative muscle fiber specification via PGC-1? and AMPK activation. Int J Biochem Cell Biol 45:1155-64
Guo, Tingqing; Bond, Nichole D; Jou, William et al. (2012) Myostatin inhibition prevents diabetes and hyperphagia in a mouse model of lipodystrophy. Diabetes 61:2414-23
Allen, David L; Hittel, Dustin S; McPherron, Alexandra C (2011) Expression and function of myostatin in obesity, diabetes, and exercise adaptation. Med Sci Sports Exerc 43:1828-35
Savage, Kathleen J; McPherron, Alexandra C (2010) Endurance exercise training in myostatin null mice. Muscle Nerve 42:355-62
McPherron, Alexandra C (2010) METABOLIC FUNCTIONS OF MYOSTATIN AND GDF11. Immunol Endocr Metab Agents Med Chem 10:217-231
Guo, Tingqing; Jou, William; Chanturiya, Tatyana et al. (2009) Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. PLoS One 4:e4937