title: Antiobesity effect of a melanin-concentrating hormone 1 receptor antagonist in diet-induced obese mice.
abstract: Melanin-concentrating hormone (MCH) is a cyclic orexigenic peptide expressed in the lateral hypothalamus, which plays an important role in regulating energy balance. To elucidate the physiological role of MCH in obesity development, the present study examined the effect of a selective MCH1 receptor (MCH1R) antagonist in the diet-induced obesity mouse model. The MCH1R antagonist has high affinity and selectivity for MCH-1R and potently inhibits intracerebroventricularly injected MCH-induced food intake in Sprague Dawley rats. Chronic intracerebroventricular infusion of the MCH1R antagonist (7.5 microg/d) completely suppressed body weight gain in diet-induced obese mice during the treatment periods and significantly decreased cumulative food intake, by 14%. Carcass analysis showed that the MCH1R antagonist resulted in a selective decrease of body fat in the diet-induced obese mice. In addition, the MCH1R antagonist ameliorated the obesity-related hypercholesterolemia, hyperinsulinemia, hyperglycemia, and hyperleptinemia. These results indicate that MCH has a major role in the development of diet-induced obesity in mice and that a MCH1R antagonist might be a useful candidate as an antiobesity agent.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba 300-2611, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mashiko
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Akira
authors.initials: A
authors.lastname: Gomori
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Moriya
authors.forename: Makoto
authors.initials: M
authors.lastname: Ito
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuda
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.forename: Zhu
authors.initials: Z
authors.lastname: Shen
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Marsh
authors.forename: Maria A
authors.initials: MA
authors.lastname: Bednarek
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: MacNeil
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004032:Diet; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D006801:Humans; D007028:Hypothalamic Hormones / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008543:Melanins / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D010907:Pituitary Hormones / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000172:deficiency; D015430:Weight Gain / Q000187:drug effects
chemical_list: D007028:Hypothalamic Hormones; C103263:MCHR1 protein, human; D008543:Melanins; D010907:Pituitary Hormones; D017481:Receptors, Somatostatin; C019463:melanin-concentrating hormone