Role of p66shc in skeletal muscle function.

p66shc is a growth factor adaptor protein that contributes to mitochondrial ROS production. p66shc is involved in insulin signaling and its deletion exerts a protective effect against diet-induced obesity. In light of the role of skeletal muscle activity in the control of systemic metabolism and obesity, we investigated which is the contribution of p66shc in regulating muscle structure and function. Here, we show that p66shc(-/-) muscles are undistinguishable from controls in terms of size, resistance to denervation-induced atrophy, and force. However, p66shc(-/-) mice perform slightly better than wild type animals during repetitive downhill running. Analysis of the effects after placing mice on a high fat diet (HFD) regimen demonstrated that running distance is greatly reduced in obese wild type animals, but not in overweight-resistant p66shc(-/-) mice. In addition, muscle force measured after exercise decreases upon HFD in wild type mice while p66shc(-/-) animals are protected. Our data indicate that p66shc affect the response to damage of adult muscle in chow diet, and it determines the maintenance of muscle force and exercise performance upon a HFD regimen.