Endocannabinoid receptor CB2 in nonalcoholic fatty liver disease

Background and Aim: Fatty infiltration and fibrosis are major issues in chronic liver disease. Recent reports suggest a role for the endocannabinoid system in these processes. Aim: To characterize localization and expression of CB2 in normal liver and nonalcoholic fatty liver. Methods: We studied 64 liver biopsies: eight were considered normal; 56 had a diagnosis of nonalcoholic fatty liver disease (NAFLD); 32 with nonalcoholic steatosis and 24 nonalcoholic steatohepatitis (NASH). CB2 immunolocalization was studied in 38 samples in paraffin blocks using immunohistochemistry, and a computerized semiquantitative analysis was carried out. CB2 mRNA expression was assessed through RT-PCR in 26 frozen liver samples and the ratio CB2/beta-actin was used to evaluate differences between groups. Statistical analysis was performed with central tendency measures and the Mann-Whitney U-test. We considered as significant differences those with a P-value < 0.05. Results: Neither parenchymal nor nonparenchymal cells in normal liver tissue react towards anti-CB2 antibodies. All the samples from patients with steatosis and nonalcoholic steatohepatitis showed hepatocellular immunoreactivity. Cholangiocytes were positive only in the NAFLD group. Normal liver tissue showed a normalized CB2/beta-actin ratio of 0.001 +/- 0.01, steatosis 6.52 +/- 17.3 (P=0.05 vs normal) and NASH 6.49 +/- 12.2 (P=0.06 vs normal and P=0.6 vs steatosis). Conclusion: CB2 receptors are expressed by hepatocytes in nonalcoholic fatty liver disease but not in normal liver.