IRS1 and obesity due to melanocortin 4 receptor deficiency: Dysregulated secretion of leptin and the increased expression of FoxO1 in propiomelanocortin (POMC) neurons provoke hyperphagia and obesity [133,134], as well as hypothalamic hyperactivation of mTORC1, seems to induce hepatic insulin resistance through the inhibition of IRS-1/AKT axis and K (ATP) channels [135,136].