Blockade of body weight gain and plasma corticosterone levels in Zucker fatty rats using an orally active neuropeptide Y Y1 antagonist

An experiment was conducted to examine whether a potent, orally active and highly selective neuropeptide Y Y1 receptor antagonist attenuates hyperphagia and obesity in genetically obese Zucker fatty rats. Oral administration of the Y1 antagonist (30 and 100 mg kg−1, once daily for 2 weeks) significa...

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Bibliographic Details
Published in:British journal of pharmacology 2002-06, Vol.136 (3), p.341-346
Main Authors: Ishihara, Akane, Kanatani, Akio, Okada, Megumu, Hidaka, Masayasu, Tanaka, Takeshi, Mashiko, Satoshi, Gomori, Akira, Kanno, Tetsuya, Hata, Mikiko, Kanesaka, Maki, Tominaga, Yushin, Sato, Naga‐aki, Kobayashi, Masahiko, Murai, Takashi, Watanabe, Keiko, Ishii, Yasuyuki, Fukuroda, Takahiro, Fukami, Takehiro, Ihara, Masaki
Format: Article
Language:English
Subjects:
Adipose Tissue - drug effects
Adipose Tissue - pathology
Administration, Oral
Analysis of Variance
Animals
Appetite Depressants - administration & dosage
Appetite Depressants - pharmacology
Biological and medical sciences
body weight gain
Cell Size - drug effects
Corticosterone - blood
Eating - drug effects
feeding behaviour
General and cellular metabolism. Vitamins
Male
Medical sciences
Models, Animal
Morpholines - pharmacology
Neuropeptide Y, a Y1 antagonist
obesity
Obesity - drug therapy
Obesity - metabolism
Obesity - physiopathology
Pharmacology. Drug treatments
plasma corticosterone levels
Rats
Rats, Zucker
Receptors, Neuropeptide Y - antagonists & inhibitors
Thiazoles - pharmacology
Weight Gain - drug effects
Zucker fatty rats
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Summary:An experiment was conducted to examine whether a potent, orally active and highly selective neuropeptide Y Y1 receptor antagonist attenuates hyperphagia and obesity in genetically obese Zucker fatty rats. Oral administration of the Y1 antagonist (30 and 100 mg kg−1, once daily for 2 weeks) significantly suppressed the daily food intake and body weight gain in Zucker fatty rats accompanied with a reduction of fat cell size and plasma corticosterone levels. Despite the fact that food intake was gradually returned to near the control level, the body weight of the treated animals remained significantly less when compared to that of the controls for the duration of the treatment. These results suggest that the Y1 receptor, at least in part, participate in pathophysiological feeding and/or fat accumulation observed in Zucker fatty rats. Y1 antagonists might be useful for the treatment of obesity. British Journal of Pharmacology (2002) 136, 341–346; doi:10.1038/sj.bjp.0704696
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0704696