Effects of chronic celiprolol treatment on brown fat, feeding, and drinking in fa/fa Zucker rats.
Celiprolol is a novel beta-adrenoceptor blocking drug that displays clinically favorable effects on glucose and lipid metabolism. Because some other atypical beta-adrenoceptor blocking drugs have been described to act as agonists on beta(3)-adrenoceptors, we aimed to investigate the effects of celiprolol on brown fat and beta(3)-adrenoceptors. Chronic treatment of obese fa/fa Zucker rats with celiprolol (50 mg/kg/day orally for 20 days) increased GDP binding to brown fat mitochondria by 1.5-fold, whereas beta(3)-adrenoceptor agonist ZD7114 ((S)-4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]-N-(2-methoxyet hyl )phenoxyacetamide, 3 mg/kg/day) increased the binding by 3.3-fold. Weight gain was reduced by 19% due to decreased water and food intakes in celiprolol-treated rats. Celiprolol did not activate lipolysis in rat adipocytes in vitro or stimulate human beta(3)-adrenoceptors expressed in Chinese hamster ovary cells as measured with Cytosensor microphysiometer. Therefore, celiprolol does not seem to activate brown fat via beta(3)-adrenoceptors.
Savontaus
E
E
Department of Pharmacology and Clinical Pharmacology, University of Turku, Kiinamyllynkatu 10, FIN-20520, Turku, Finland.
Rouru
J
J
Malminiemi
K
K
Luukkaa
V
V
Pesonen
U
U
Koulu
M
M
Huupponen
R
R
D002001:Adipose Tissue, Brown / Q000187:drug effects*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001833:Body Temperature Regulation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D017272:Celiprolol / Q000494:pharmacology*; D006224:Cricetinae; D004327:Drinking Behavior / Q000187:drug effects*; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007328:Insulin; D017272:Celiprolol