Nox2 deficiency in mice exacerbates the impact of HFD on body weight, body composition, and glucose tolerance and inhibits several of the beneficial metabolic adaptations to exercise [158]; this work highlights Nox2 and its ROS contributing properties as a key mediator of exercise-induced benefits to skeletal muscle in the context of diet-induced obesity. The gene discussed is CYBB; the disease is obesity due to melanocortin 4 receptor deficiency.