1. A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice
- Author
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Xiao-Ming Guan, Osamu Okamoto, Takahiro Fukuroda, Tomoyuki Ohe, Nagaaki Sato, Akira Gomori, Takehiro Fukami, Masaru Nishikibe, Yuko Mitobe, Hiroko Matsushita, Masaki Ihara, Lex M.T. Van Der Ploeg, Akio Kanatani, Naomi Murai, Hisashi Iwaasa, Masayasu Hidaka, Shin Ichiro Egashira, Takeshi Tanaka, Douglas J. MacNeil, Makoto Jitsuoka, Yasuyuki Ishii, Satoshi Mashiko, Akane Ishihara, and Takashi Murai
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Adipose tissue ,Biology ,Weight Gain ,Energy homeostasis ,Mice ,Cyclohexanes ,Internal medicine ,medicine ,Hyperinsulinemia ,Animals ,Insulin ,Neuropeptide Y ,Obesity ,Receptor ,Mice, Knockout ,Multidisciplinary ,Leptin ,Body Weight ,Antagonist ,nutritional and metabolic diseases ,Organ Size ,Biological Sciences ,medicine.disease ,Neuropeptide Y receptor ,Diet ,Rats ,Rats, Zucker ,Receptors, Neuropeptide Y ,Mice, Inbred C57BL ,Endocrinology ,Adipose Tissue ,Xanthenes ,Anti-Obesity Agents ,Diet-induced obese - Abstract
Neuropeptide Y (NPY) is thought to have a major role in the physiological control of energy homeostasis. Among five NPY receptors described, the NPY Y5 receptor (Y5R) is a prime candidate to mediate some of the effects of NPY on energy homeostasis, although its role in physiologically relevant rodent obesity models remains poorly defined. We examined the effect of a potent and highly selective Y5R antagonist in rodent obesity and dietary models. The Y5R antagonist selectively ameliorated diet-induced obesity (DIO) in rodents by suppressing body weight gain and adiposity while improving the DIO-associated hyperinsulinemia. The compound did not affect the body weight of lean mice fed a regular diet or genetically obese leptin receptor-deficient mice or rats, despite similarly high brain Y5R receptor occupancy. The Y5R antagonist acts in a mechanism-based manner, as the compound did not affect DIO of Y5R-deficient mice. These results indicate that Y5R is involved in the regulation and development of DIO and suggest utility for Y5R antagonists in the treatment of obesity.
- Published
- 2006
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