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

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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.