To further characterize the function of myostatin, in vivo metabolic assays were performed including euglycemic-hyperinsulinemic clamp studies, lipid oxidation and indirect calorimetry using wild type and myostatin null mice. We have also measured the effects of high fat and normal diets on insulin and glucose tolerance and the effects of exercise on myostatin mull mice as compared to wild type mice. We have found that myostatin null mice have improved insulin sensitivity and are resistant to weight gain and the development of insulin resistance when placed on a high-fat diet. Mice with muscle-specific inhibition of myostatin signaling due to over-expression of a dominant negative activin type IIB receptor (Acvr2b) have a similar phenotype as myostatin null mice. These results show that the improved insulin sensitivity, reduction of adipose mass, and resistance to diet-induced obesity seen in myostatin null mice can be explained by the loss of myostatin on muscle alone.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2009
Total Cost
$479,523
Indirect Cost
City
State
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Zip Code
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
McPherron, Alexandra C (2010) METABOLIC FUNCTIONS OF MYOSTATIN AND GDF11. Immunol Endocr Metab Agents Med Chem 10:217-231
Savage, Kathleen J; McPherron, Alexandra C (2010) Endurance exercise training in myostatin null mice. Muscle Nerve 42:355-62
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