title: Blockade of body weight gain and plasma corticosterone levels in Zucker fatty rats using an orally active neuropeptide Y Y1 antagonist.
abstract: 1. 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. 2. Oral administration of the Y1 antagonist (30 and 100 mg x 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. 3. 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. 4. 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.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba, Ibaraki 300-2611, Japan. ishihraan@bsnyu.co.jp
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Megumu
authors.initials: M
authors.lastname: Okada
authors.forename: Masayasu
authors.initials: M
authors.lastname: Hidaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mashiko
authors.forename: Akira
authors.initials: A
authors.lastname: Gomori
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kanno
authors.forename: Mikiko
authors.initials: M
authors.lastname: Hata
authors.forename: Maki
authors.initials: M
authors.lastname: Kanesaka
authors.forename: Yushin
authors.initials: Y
authors.lastname: Tominaga
authors.forename: Naga-aki
authors.initials: NA
authors.lastname: Sato
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Murai
authors.forename: Keiko
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuroda
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
authors.forename: Masaki
authors.initials: M
authors.lastname: Ihara
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D004435:Eating / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009025:Morpholines / Q000494:pharmacology*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: C467806:6-(5-ethyl-1,3-thiazol-2-ylthiomethyl)-2-(3-methoxy-5-(2-propenyloxycarbonylamino)benzylamino)-4-morpholinopyridine; D001067:Appetite Depressants; D009025:Morpholines; D017476:Receptors, Neuropeptide Y; D013844:Thiazoles; C097212:neuropeptide Y-Y1 receptor; D003345:Corticosterone