Second, we also found that exercise training in the obese mice protected against an obesity-associated increase in mitochondria-mediated apoptotic signaling (e.g., Bax/Bcl-2 ratio, mPTP opening sensitivity, and cytochrome c level) and apoptosis (cleaved caspase-3-positive cells and TUNEL-positive myonuclei) in their skeletal muscle. The gene discussed is CYCS; the disease is obesity due to melanocortin 4 receptor deficiency.