CB1 blockade-induced weight loss over 48 weeks decreases liver fat in proportion to weight loss in humans

OBJECTIVE: Studies in mice have suggested that endocannabinoid blockade using the cannabinoid receptor type 1 (CB1) blocker rimonabant prevents obesity-induced hepatic steatosis. DESIGN AND SUBJECTS: To determine effects of rimonabant on liver fat in humans, we measured liver fat content by proton magnetic resonance spectroscopy in 37 subjects who used either a CB1 blocker rimonabant or placebo in a double-blind, randomized manner. This was retrospectively compared with a historical hypocaloric diet weight loss group (n=23). RESULTS: Weight loss averaged 8.5 +/- 1.4 kg in the rimonabant, 1.7 +/- 1.0 kg in the placebo and 7.5 +/- 0.2 kg in the hypocaloric diet group (P < 0.001, rimonabant vs placebo; NS, rimonabant vs hypocaloric diet). Liver fat decreased more in the rimonabant (5.9% (2.5-14.6%) vs 1.8% (0.9-3.5%), before vs after) than in the placebo group (6.8% (2.2-15.7%) vs 4.9% (1.6-7.8%), before vs after, P < 0.05). The percentage change in body weight correlated closely with the percentage loss of liver fat (r=0.70, P > 0.0001). The decreases in liver fat were comparable between the rimonabant and the young historical hypocaloric diet groups. CONCLUSIONS: We conclude that, unlike in mice, in humans rimonabant decreases liver fat in proportion to weight loss.