The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance

SPECIFIC AIMSThe aim of the present study was to unravel the molecular events involved in the reduction of adipose mass by the selective central cannabinoid CB1 receptor antagonist, SR141716. We used a transcriptional approach and characterized gene modulations in adipose tissues of SR141716-treated diet-induced obese mice, a mouse model that closely resembles human obesity. Thereby, we identified the metabolic pathways mediating the sustained long term anti-obesity effect of this molecule.PRINCIPAL FINDINGS1. SR141716 reversed the obese adipocyte phenotypeC57BL/6J mice were fed either a standard (STD) or a high fat diet (HFD) for 12 wk and then were treated with SR141716 at 10 mg/kg/day p.o. for 40 days. The treatment resulted in a remarkable reduction of body weight by –18% in HFD mice treated with SR141716 compared with vehicle-treated HFD mice. Lumbar white fat (WAT) and brown fat (BAT) adipose tissue appeared to be the primary peripheral targets of the drug effect since their weight were both reduced...