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Blockade of MCH1 receptor signalling ameliorates obesity and related hepatic steatosis in ovariectomized mice
Author(s) -
Gomori A,
Ishihara A,
Ito M,
Matsushita H,
Ito M,
Mashiko S,
Iwaasa H,
Matsuda M,
Bednarek M A,
Qian S,
MacNeil D J,
Kanatani A
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707292
Subject(s) - medicine , endocrinology , orexigenic , ovariectomized rat , fatty liver , steatosis , receptor , triglyceride , lipogenesis , chemistry , biology , adipose tissue , hormone , neuropeptide , neuropeptide y receptor , cholesterol , disease
Background and purpose: Melanin‐concentrating hormone (MCH) is a cyclic orexigenic neuropeptide predominantly expressed in the lateral hypothalamus. We investigated the roles of MCH1 receptor signalling in ovariectomy (OVX)‐induced obesity in female C57BL/6J mice, an animal model of postmenopausal obesity. Experimental approach: The effects of blocking signalling via the MCH1 receptor on OVX‐induced obesity was investigated by using Mch1r deficient (KO) mice and chronic treatment with a selective MCH1 receptor antagonist. Key results: OVX induced body weight gain and increases in the weight of visceral fat and of liver; these effects were attenuated following OVX in Mch1r KO mice. OVX‐induced triglyceride (TG) accumulation and elevated expression of lipogenic genes were significantly ameliorated in the liver of Mch1r KO mice. In agreement with these results, chronic i.c.v. infusion of a selective MCH1 receptor antagonist significantly reduced body weight gain, visceral fat and liver weights in OVX mice, and hepatic TG contents and lipogenic gene expression levels were normalized. Conclusion and implications: Our results indicate that MCH1 receptor signalling is involved in the development of fatty liver, as well as obesity, in OVX mice, and suggest a therapeutic potential for MCH1 receptor antagonists in the treatment of obesity and fatty liver. British Journal of Pharmacology (2007) 151 , 900–908; doi: 10.1038/sj.bjp.0707292