Cannabinoid receptors as novel therapeutic targets for the management of non-alcoholic steatohepatitis

Prevalence of non-alcoholic steatohepatitis (NASH) rises steadily in Western countries with the obesity epidemic. NASH is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. The cannabinoid system is increasingly emerging as a crucial mediator Of acute and chronic liver injury. Recent experimental and clinical data indicate that peripheral activation of cannabinoid CB I receptors promotes insulin resistance and liver steatogenesis, two key steps in the pathogenesis of non-alcoholic fatty liver disease. Moreover, CB I receptors enhance progression of liver fibrogenesis. These findings provide a strong rationale for the use of CB I antagonists in the management of NASH. (C) 2008 Elsevier Masson SAS. All rights reserved.