Sibutramine sensitivity assay revealed a unique phenotype of bombesin BB3 receptor-deficient mice.
Sibutramine sensitivity assay in genetically obese (bombesin BB3 receptor (BRS-3)-deficient mice, KK-Ay mice, db/db mice and Zucker obese rat) and wild-type animals was examined. The sensitivity of Sibutramine (10 mg/kg, p.o.) in BRS-3-deficient mice was retained as well as normal animals; however, it was decreased in KK-Ay, db/db mice and Zucker obese rat. The suppression values of food intake in BRS-3-deficient, KK-Ay, db/db mice and Zucker obese rat were 49.8+/-5.8%, 16.1+/-4.7%, 0.1+/-2.8% and -2.0+/-2.2% (mean +/- S.E.), respectively. Next, we found that the contribution of hyperphagia was small in the progress of obesity in BRS-3-deficient mice by calculating energy efficiency. Our results indicate that there is an inverse relationship between the sensitivity to Sibutramine and the contribution of hyperphagia to the progress of obesity in animals.
Matsumoto
Kouji
K
Department of Pharmaceuticals Research Laboratory, Mitsubishi Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama-City, Kanagawa 227-0033, Japan. Matsumoto.Kouji@mk.m-pharma.co.jp
Iijima
Hiroaki
H
D000818:Animals; D001067:Appetite Depressants / Q000627:therapeutic use*; D003503:Cyclobutanes / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D006963:Hyperphagia / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000188:drug therapy / Q000235:genetics; D010641:Phenotype; D051381:Rats; D011924:Rats, Zucker; D018004:Receptors, Bombesin / Q000172:deficiency* / Q000235:genetics; D013045:Species Specificity; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics
D001067:Appetite Depressants; D003503:Cyclobutanes; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3; C058254:sibutramine