title: A pair-feeding study reveals that a Y5 antagonist causes weight loss in diet-induced obese mice by modulating food intake and energy expenditure.
abstract: Neuropeptide Y (NPY) is thought to have a significant role in the physiological control of energy homeostasis. We recently reported that an NPY Y5 antagonist inhibits body weight gain in diet-induced obese (DIO) mice, with a moderate reduction in food intake. To clarify the mechanism of the antiobesity effects of the Y5 antagonist, we conducted a pair-feeding study in DIO mice. The Y5 antagonist at 100 mg/kg produced a moderate feeding suppression leading to an 18% decrease in body weight, without altering body temperature. In contrast, the pair-fed group showed only a transient weight reduction and a reduced body temperature, thus indicating that the Y5 antagonist stimulates thermogenesis. The Y5 antagonist-treated mice showed an up-regulation of uncoupling protein mRNA in brown adipose tissue (BAT) and white adipose tissue (WAT), suggesting that both BAT and WAT contribute to energy expenditure. Thus, the Y5 antagonist induces its antiobesity effects by acting on both energy intake and expenditure.
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: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Hideki
authors.initials: H
authors.lastname: Sano
authors.forename: Junko
authors.initials: J
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Gomori
authors.forename: Zenjun
authors.initials: Z
authors.lastname: Oda
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Moriya
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsushita
authors.forename: Makoto
authors.initials: M
authors.lastname: Jitsuoka
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: MacNeil
authors.forename: Lex H T
authors.initials: LH
authors.lastname: Van der Ploeg
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D001831:Body Temperature; D004032:Diet; D004435:Eating / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D007473:Ion Channels / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics; D009765:Obesity / Q000188:drug therapy; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D000071256:Uncoupling Protein 1; D015854:Up-Regulation / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D017476:Receptors, Neuropeptide Y; D000071256:Uncoupling Protein 1; C100568:neuropeptide Y5 receptor