POMC and obesity due to melanocortin 4 receptor deficiency: Specifically, in the hypothalamic region of the brain, elevated UPR activity has been shown to potentiate diet-induced obesity (17, 20–23) and mice overexpressing UPR effector X-box binding protein 1 (XBP1) in POMC neurons are resistant to diet-induced obesity via cell- and non–cell-autonomous mechanisms (24).