Hepatic Expression of Endocannabinoid Receptors (CB1 and CB2) in Patients with Non-Alcoholic Steatohepatitis and Its Relationship with Metabolic Syndrome

The pathogenetic pathways in the progression from steatosis to NASH have not yet been fully elucidated. Recent studies reported that the endocannabinoid system has a role in a variety of steps during chronic liver disease. Endocannabinoids are endogenous lipid mediators with a mechanism of action through activating cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Stimulation of the CB1 receptors increases hepatic fatty acid synthesis. Expression of CB2 receptors in fatty liver may be indicative of their association with metabolic syndrome. The fact that the endocannabinoid system activates various metabolic functions in peripheral tissues suggests that this system may play a role in the treatment of various diseases. In this study, we examined whether metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) are associated with expression of cannabinoid receptors. Fifty-four individuals with nonalcoholic steatohepatitis (NASH) and 17 with steatosis based on pathology reports of liver biopsies were included in the patient group. Forty individuals whose liver tissue samples revealed hemangioma, focal nodules and/or simple cyst, and liver areas and liver tissues that were normal in pathology reports were selected as the control group. The association between cannabinoid receptor-1 (CB-1R) and -2 (CB-2R) expression, determined immunohistochemically, and metabolic syndrome criteria and NAS score were determined. A comparison of control (n = 40), steatosis (n = 17)and NASH groups (n = 54) revealed a significant difference in CB-2R expression between patients with steatosis and patients withNASH. The expression of CB-2 receptor in the steatosis group was statistically significantly higher than in the NASH group (p = 0.017). But showed no significant difference in CB-2R expression between NAFLD and control groups (p = 0.924). In our study, it was determined thatCannabinoid receptors-2 (CB-2Rs) were expressed in the liver cells of all patients and the control groups. In addition, the expression of thesereceptors was found to be associated with various parameters such as arterial hypertension, obesity, hyperlipidemia and lobularinflammation.