[Regulation of appetite by melanocortin and its receptors].
alpha, beta, gamma-MSH and ACTH are derived from the same precursor, POMC(proopiomelanocortin), and are classified as melanocortin. alpha-MSH plays an important role in the regulation of appetite and energy expenditure via central melanocortin receptor, melanocortin 4 receptor(MC4R), which is expressed mainly in hypothalamus. alpha-MSH or its analogue shows inhibitory effect on appetite and inversely MC4R antagonist stimulates appetite. MC4R knock-out mice has adult-onset obesity and decreased energy expenditure. POMC gene expression in hypothalamus is partially regulated by leptin. Agouti-related peptide(AgRP), a homologue of agouti peptide and antagonist of MC3R and MC4R, is expressed in human brain and may act as a inhibitor of alpha-MSH. From the genetical aspect, the region near POMC gene, 2p23, is one of the susceptibility loci of human obesity. POMC gene mutations are found in two families, where mutations in both alleles cause human obesity, red hair, adrenal dysfunction, due to alpha-MSH and ACTH deficiencies. In morbidity obese patients, heterozygous MC4R gene mutations are found among 4% of them. These results suggest the importance of melanocortin and its receptors on appetite regulation in human.
Mori
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Genetique des Maladies Multifactorielles, Institut de Biologie de Lille-Institut Pasteur de Lille.
D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000502:physiology*; D011979:Receptors, Pituitary Hormone / Q000502:physiology*
D011979:Receptors, Pituitary Hormone; C029446:MSH receptor; D009074:Melanocyte-Stimulating Hormones