苏州房屋均价:翻译(有分吆,翻译的好还加分呢???!!我有的是分)

Melanocortins are peptides (such as -MSH) that are cleaved from the pro-opiomelanocortin (POMC) precursor molecule and that exert their effects by binding to members of a family of melanocortin receptors49. A role for melanocortin signalling in the control of energy homeostasis first emerged after the cloning of the MC3- and MC4-receptor genes and the demonstration that they are expressed primarily in the brain54. This discovery was followed by evidence that a synthetic agonist of these receptors suppresses food intake, whereas a synthetic antagonist has the opposite effect55. The report that mice lacking the MC4 receptor (owing to gene targeting) are hyperphagic and very obese56 indicates that tonic signalling by MC4 receptors limits food intake and body fat mass. Mice heterozygous for the deleted MC4 allele also become obese, although less so than homozygous knockouts56. Lack of a full complement of central MC4 receptors, therefore, predisposes to hyperphagia and pathologicalweightgain.This finding has since been extended to humans with MC4-receptor mutations4,5.
Further evidence for the importance of melanocortin signalling came from studies of agouti (Ay/a) mice, an autosomal dominant model of genetic obesity characterized by a yellow coat colour and an obese phenotype. Cloning of the agouti gene57 identified a protein (‘agouti’) that functions as an antagonist of cutaneous MC1 receptors and normally is expressed by hair follicles. By reducing MC1 signalling, increased cutaneous agouti lightens the coat colour. Agouti mice, however, express agouti in tissues throughout the body and consequently develop both a yellow coat colour and obesity(owingtoectopicagoutiproductionwithinthebrain,whereitantagonizes MC4 receptors)49 (Fig. 2b).