TY - JOUR T1 - A Pair-Feeding Study Reveals That a Y5 Antagonist Causes Weight Loss in Diet-Induced Obese Mice by Modulating Food Intake and Energy Expenditure JF - Molecular Pharmacology JO - Mol Pharmacol SP - 602 LP - 608 DO - 10.1124/mol.106.029991 VL - 71 IS - 2 AU - Satoshi Mashiko AU - Akane Ishihara AU - Hisashi Iwaasa AU - Hideki Sano AU - Junko Ito AU - Akira Gomori AU - Zenjun Oda AU - Ryuichi Moriya AU - Hiroko Matsushita AU - Makoto Jitsuoka AU - Osamu Okamoto AU - Douglas J. MacNeil AU - Lex H. T. Van der Ploeg AU - Takehiro Fukami AU - Akio Kanatani Y1 - 2007/02/01 UR - http://molpharm.aspetjournals.org/content/71/2/602.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -