CASP3 and obesity due to melanocortin 4 receptor deficiency: In addition, although our study has a technical limitation in distinguishing between physiological apoptosis and pathological apoptosis, we found that aerobic exercise training for 12 weeks attenuated obesity-induced mitochondria-mediated apoptotic signaling (e.g., Bax, mPTP opening sensitivity, cytochrome c level, and cleaved caspase-3-positive cells) and apoptosis (e.g., TUNEL-positive myonuclei) in the skeletal muscle, suggesting that aerobic exercise training inhibits obesity-induced reduction of skeletal muscle mass.