Huszar D, Lynch C A, Fairchild-Huntress V, Dunmore J H, Fang Q, Berkemeier L R, Gu W, Kesterson R A, Boston B A, Cone R D, Smith F J, Campfield L A, Burn P, Lee F
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
Cell. 1997 Jan 10;88(1):131-41. doi: 10.1016/s0092-8674(00)81865-6.
The melanocortin-4 receptor (MC4-R) is a G protein-coupled, seven-transmembrane receptor expressed in the brain. Inactivation of this receptor by gene targeting results in mice that develop a maturity onset obesity syndrome associated with hyperphagia, hyperinsulinemia, and hyperglycemia. This syndrome recapitulates several of the characteristic features of the agouti obesity syndrome, which results from ectopic expression of agouti protein, a pigmentation factor normally expressed in the skin. Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R.
黑皮质素-4受体（MC4-R）是一种G蛋白偶联的七跨膜受体，在大脑中表达。通过基因靶向使该受体失活会导致小鼠出现与食欲亢进、高胰岛素血症和高血糖相关的成年起病型肥胖综合征。该综合征概括了刺鼠肥胖综合征的几个特征，刺鼠肥胖综合征是由刺鼠蛋白的异位表达引起的，刺鼠蛋白是一种通常在皮肤中表达的色素沉着因子。我们的数据确定了小鼠体重调节中的一条新信号通路，并支持一种模型，即刺鼠诱导肥胖的主要机制是对MC4-R的慢性拮抗作用。
