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 CB1 receptors promotes insulin resistance and liver steatogenesis, two key steps in the pathogenesis of non-alcoholic fatty liver disease. Moreover, CB1 receptors enhance progression of liver fibrogenesis. These findings provide a strong rationale for the use of CB1 antagonists in the management of NASH.
Mallat
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Inserm, U841, Créteil, F-94010 France. ariane.mallat@hmn.aphp.fr
Lotersztajn
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D001095:Arachidonic Acids / Q000627:therapeutic use*; D002186:Cannabinoids / Q000627:therapeutic use; D063388:Endocannabinoids; D005234:Fatty Liver / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D053284:Polyunsaturated Alkamides / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000187:drug effects*
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; C078814:anandamide