title: Effect of the cannabinoid receptor-1 antagonist rimonabant on lipolysis in rats.
abstract: The cannabinoid receptor 1 antagonist, rimonabant, reduces food intake and body weight, but contradictory findings have been reported as to whether the weight-reducing effect is fully accounted for by the reduced food intake or if rimonabant also mediates a lipolytic effect. In the present study, the effect on weight loss was studied in diet-induced obese rats after 3 days and 3 weeks of exposure to rimonabant, respectively. Induction of lipolysis was examined following acute administration and following 3 weeks of repeated dosing. Rimonabant-treated rats lost significantly more weight than their food-restricted controls. This effect was most pronounced in the beginning of the treatment period. No increase in lipolytic activity was found after 3 weeks of repeated dosing as measured by microdialysis in adipose tissue whereas acute administration of 10mg/kg produced a significant increase in microdialysate levels of glycerol illustrating an acute stimulation of lipolysis. No equivalent increase in glycerol was, however, observed in vitro following incubation of isolated rat adipocytes with rimonabant. This finding excludes a direct lipolytic action of rimonabant on tissue level. Instead, administration of 10mg/kg produced a significant increase in noradrenaline excretion in diet-induced obese rats, suggesting an increase in sympathoadrenal activity. In conclusion, the present study suggests an acute lipolytic effect of rimonabant mediated through activation of the sympathoadrenal system.
authors: Diabetes & Obesity Pharmacology, Novo Nordisk A/S, Denmark. Signe.mlhj@gmail.com
authors: Signe
authors: S
authors: Mølhøj
authors: Harald S
authors: HS
authors: Hansen
authors: Martina
authors: M
authors: Schweiger
authors: Robert
authors: R
authors: Zimmermann
authors: Thue
authors: T
authors: Johansen
authors: Kjell
authors: K
authors: Malmlöf
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000652:urine; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D013997:Time Factors
chemical_list: C543264:Cnr1 protein, rat; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant; D009638:Norepinephrine