Antagonism of central melanocortin receptors in vitro and in vivo by Agouti-related protein
Antagonism of central melanocortin receptors in vitro and in vivo by Agouti-related protein
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DOI：
10.1126/science.278.5335.135
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发表时间：
1997-10-03
期刊：
影响因子：
56.9
通讯作者：
Barsh, GS
中科院分区：
文献类型：
--
作者：
Ollmann, MM;Wilson, BD;Barsh, GS
Agglutinase蛋白的表达通常限于皮肤，在那里它影响色素沉着，但无处不在的表达导致肥胖。鉴定了编码Agouti相关蛋白的表达序列标签，其RNA通常在下丘脑中表达，并且其水平在ob/ob小鼠中增加了8倍。重组Agoutirelated蛋白是一种强效的、选择性的黑皮质素受体亚型Mc 3r和Mc 4 r的拮抗剂，在转基因小鼠中普遍表达人AGRP互补DNA引起肥胖而不改变色素沉着，因此Agoutirelated蛋白是一种在瘦素信号下游参与正常体重控制的神经肽。
Expression of Agouti protein is normally limited to the skin where it affects pigmentation, but ubiquitous expression causes obesity. An expressed sequence tag was identified that encodes Agouti-related protein, whose RNA is normally expressed in the hypothalamus and whose levels were increased eightfold in ob/ob mice. Recombinant Agoutirelated protein was a potent, selective antagonist of Mc3r and Mc4r, melanocortin receptor subtypes implicated in weight regulation, Ubiquitous expression of human AGRP complementary DNA in transgenic mice caused obesity without altering pigmentation, Thus, Agouti-related protein is a neuropeptide implicated in the normal control of body weight downstream of leptin signaling.