Mutations in melanocortin-4 receptor: From fish to men

Melanocortin-4 receptor (MC4R), expressed abundantly in the hypothalamus, is a critical regulator of energy homeostasis, including both food intake and energy expenditure. Shortly after the publication in 1997 of the Mc4r knockout phenotypes in mice, including increased food intake and severe obesity, the first mutations in MC4R were reported in humans in 1998. Studies in the subsequent two decades have established MC4R mutation as the most common monogenic form of obesity, especially in early-onset severe obesity. Studies in animals, from fish to mammals, have established the conserved physiological roles of MC4R in all vertebrates in regulating energy balance. Drug targeting MC4R has been recently approved for treating morbid genetic obesity. How the MC4R can be exploited for animal production is highly worthy of active investigation.