Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity

The neural melanocortin receptors, melanocortin-3 and -4 receptors (MC3R and MC4R), have been shown to regulate different aspects of energy homeostasis in rodents. Human genetic studies showed that mutations in the MC4R gene are the most common monogenic form of obesity. Functional analyses of the mutant receptors revealed multiple defects. A classification scheme is presented for cataloguing the ever-increasing array of MC4R mutations. Functional analysis of the only inactivating MC3R mutation is also summarized. Insights from the analyses of the naturally occurring mutations in the MC3R and MC4R on the structure and function of these receptors are highlighted.