Mutations in the melanocortin-4 receptor (MC4R) in humans are the single most common cause of rare monogenic 1severe obesity, and polymorphisms in this gene are also associated with obesity in the gen Show more
Mutations in the melanocortin-4 receptor (MC4R) in humans are the single most common cause of rare monogenic 1severe obesity, and polymorphisms in this gene are also associated with obesity in the general population. The MC4R is a G-protein coupled receptor, and in vitro analysis suggests that MC4R can signal through several different G-protein subtypes. In vivo studies show complex outcomes, with different G-proteins in different cells responsible for different physiological responses linked to obesity. There is an emerging consensus that Gαq-linked signals in the paraventricular nucleus of the hypothalamus are essential for normal satiety and the control of feeding behavior. Many MC4R mutations have been analyzed for the molecular defect underlying their association with obesity, which has revealed a group - referred to as class V mutants - with no measurable change in receptor function. However, Gαq-linked signaling leading to Ca Show less