A pair-feeding study reveals that a Y5 antagonist causes weight loss in diet-induced obese mice by modulating food intake and energy expenditure.
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.
Mashiko
Satoshi
S
Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo 3, Tsukuba 300-2611, Japan.
Ishihara
Akane
A
Iwaasa
Hisashi
H
Sano
Hideki
H
Ito
Junko
J
Gomori
Akira
A
Oda
Zenjun
Z
Moriya
Ryuichi
R
Matsushita
Hiroko
H
Jitsuoka
Makoto
M
Okamoto
Osamu
O
MacNeil
Douglas J
DJ
Van der Ploeg
Lex H T
LH
Fukami
Takehiro
T
Kanatani
Akio
A
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*
D007473:Ion Channels; D024101:Mitochondrial Proteins; D017476:Receptors, Neuropeptide Y; D000071256:Uncoupling Protein 1; C100568:neuropeptide Y5 receptor