Effect of myostatin inhibition on skeletal muscle gene expression in high fat diet-fed mice

Myostatin (GDF8) is a member of the TGF-beta family of proteins which is predominantly expressed in skeletal muscle and acts as a negative regulator of muscle mass. Inhibition of myostatin leads to muscle hypertrophy and has been shown to mitigate insulin resistance in mouse models of type 2 diabetes, although the mechanisms underlying this effect are unclear. We found that myostatin inhibition by AAV-mediated overexpression of the myostatin propeptide improves skeletal muscle insulin sensitivity in mice made insulin-resistant by high fat diet feeding. To gain insight into potential gene expression changes responsible for this effect, we performed microarray analysis on skeletal muscle samples from high fat diet-fed mice with and without myostatin inhibition. Male C57Bl/6 mice (n=8) were switched from regular chow to a high fat diet (HFD) at 8 weeks of age. 4 Weeks later, mice were given an intramuscular injection of AAV8 Promyo into one Tibialis Cranialis (TC) muscle, while the contralateral TC muscle was injected with saline. Mice were kept for 10 weeks post-injection before collecting the injected muscles.