The Central Melanocortin System and Energy Homeostasis.

Obesity is a significant health problem owing to increased risk for diabetes and cardiovascular disease, and several lines of evidence suggest that alterations in the central melanocortin system might account for some of the genetic contribution to obesity in humans. First, the phenotypic aspects and dominant inheritance of the melanocortin obesity syndromes in the mouse are more like human obesity than other murine obesity syndromes. Second, studies recently published present two rare cases of familial obesity resulting from null alleles of the proopiomelanocortin (POMC) gene, providing the first evidence that the melanocortin pathway in humans subserves the same function in regulation of energy homeostasis as it does in the rodent. Additional studies suggest that heterozygous mutations in the melanocortin 4 receptor might be a common reason for genetic predisposition to obesity in children. Research on the central melanocortin system in rodents suggests that this system might be a fundamental component of the adipostat, the mechanism by which energy stores are held relatively constant, and this hypothesis will be the focus of this review.