The mechanism of anorectic effect from MCH1R antagonism in the peripheral tissue

我们开发了一种非肽拮抗剂甲黑色素浓缩激素受体1 (MCH1R), TPI1361-17 （TPI）。TPI不跨越血脑屏障，腹腔内给药引起小鼠明显的厌食作用，提示MCH系统不仅局限于中枢神经系统，还存在于外周组织。口服葡萄糖负荷降低循环中的MCH水平。在饮食诱导的肥胖小鼠中，TPI降低了体重、食物摄入量，并改善了胰岛素抵抗。这些结果表明MCH系统定位于外周组织，并可能调节能量稳态。

We have developed a non-peptide antagonist formelanin-concentrating hormone receptor 1 (MCH1R), TPI1361-17 (TPI). TPI does not crossblood brain barrier, and the intra-peritoneal administration cause prominent anorexiceffect in mice, which suggest MCH system localize in peripheral tissues, as well as incentral nervous systems. Oral glucose load reduced MCH level in circulation. In thediet-induced obese mice, TPI reduced body weight, food intake, and improved insulinresistance. These results suggest that MCH system localize in peripheral tissues and itmay regulate energy homeostasis.