Reply:

Abstract

We thank Rossi and colleagues for their interest in our experimental findings delineating the impact of CB2 receptors in experimental models of liver injury. We reported recently that the hepatic cannabinoid receptor 2 (CB2) displays beneficial hepatoprotective and antifibrogenic properties.1, 2 However, as stressed by Rossi and colleagues, we also demonstrated that treatment of obese mice with the CB2-selective agonist JWH-133 enhances insulin resistance and steatosis.3 Deleterious effects of CB2 agonism in obese mice were attributed to a proinflammatory effect of adipose tissue CB2 receptors.3 However, our recent findings in a model of alcoholic liver injury indicate that stimulation of hepatic CB2 receptors reduces the development of fatty liver.4 Altogether, our experimental data demonstrate the protective effects of hepatic CB2 receptors against liver injury, steatosis, and fibrosis. In their cohort study of over 400 obese children, Rossi and colleagues show a positive correlation between the presence of a CB2 variant with reduced activity, as assessed in culture studies, and the degree of liver injury estimated by serum aminotransferase levels. These interesting findings constitute the first evidence supporting the clinical relevance of hepatoprotective effects of CB2 receptors. Further studies should be conducted to examine the impact of CB2 polymorphism on the severity of liver lesions (steatosis, necroinflammation, and fibrosis) in patients with nonalcoholic steatohepatitis. Sophie Lotersztajn* , Fatima Teixeira-Clerc*, Vanessa Deveaux*, Sylvie Manin*, Ariane Mallat* , * INSERM U955, Créteil France, Université Paris Est, Créteil France