Blockade of body weight gain and plasma corticosterone levels in Zucker fatty rats using an orally active neuropeptide Y Y1 antagonist.
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.
Ishihara
Akane
A
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba, Ibaraki 300-2611, Japan. ishihraan@bsnyu.co.jp
Kanatani
Akio
A
Okada
Megumu
M
Hidaka
Masayasu
M
Tanaka
Takeshi
T
Mashiko
Satoshi
S
Gomori
Akira
A
Kanno
Tetsuya
T
Hata
Mikiko
M
Kanesaka
Maki
M
Tominaga
Yushin
Y
Sato
Naga-aki
NA
Kobayashi
Masahiko
M
Murai
Takashi
T
Watanabe
Keiko
K
Ishii
Yasuyuki
Y
Fukuroda
Takahiro
T
Fukami
Takehiro
T
Ihara
Masaki
M
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*
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