Fatty acid flux and oxidation are increased by rimonabant in obese women

This study aimed to determine in obese women if endocannabinoid receptor antagonism has effects on fatty acid and triglyceride metabolism and insulin sensitivity which are independent from the metabolic effects of weight loss. Fourteen obese (BMI = 33.0 ± 0.5 kg/m2) (mean ± SEM) Caucasian post-menopausal women, aged 57.8 ± 4.7 years were studied. The women were randomised to 2 groups, one group received the endocannabinoid receptor antagonist rimonabant (20 mg/d) for 12 weeks. A control group achieved the same weight loss by a hypocaloric dietary intervention over 12 weeks. Palmitate production rate (Ra), a measure of lipolysis, and palmitate oxidation rate, and VLDL1 and VLDL2 triglyceride (TG) kinetics, were measured using isotopic tracers before and after the intervention. Weight loss was not different in the 2 groups; 2.6 ± 0.5 kg with rimonabant and 3.1 ± 1.0 kg in the control group. Palmitate Ra increased with rimonabant with no change in the control group (p = 0.03 between groups). Palmitate oxidation rate increased with rimonabant but decreased in the control group (p = 0.005 between groups). VLDL1 TG secretion rate decreased in the control group and increased in the rimonabant group (p = 0.008 between groups). There was no significant effect on insulin sensitivity. This study suggests that endocannabinoid receptor antagonism for 12 weeks in obese women increased lipolysis and fatty acid oxidation. The increase in VLDL1 TG secretion rate may be due to the increase in lipolysis which exceeded the increase in fatty acid oxidation.