POMC and obesity due to melanocortin 4 receptor deficiency: POMC-derived neuropeptides, including adrenocorticotropic hormone (ACTH), α/β melanocyte–stimulating hormone (α/β-MSH), and β-endorphin (5, 6), are critical for energy homeostasis, and both POMC-deficient rodent models and human patients with POMC mutations invariably exhibit hyperphagia and marked obesity (4, 7–15).