In good agreement with our findings, SESN2 expression was increased during hypernutrition in the liver and muscles and maintained metabolic homeostasis in obese livers so as to attenuate the systemic effects of IR, whereas ablation of SESN2 increased obesity-induced glucose intolerance, IR, and hepatic steatosis (53). The gene discussed is SESN2; the disease is obesity due to melanocortin 4 receptor deficiency.