Hepatic Expression of Adiponectin Receptors Increases with Non-alcoholic Fatty Liver Disease Progression in Morbid Obesity in Correlation with Glutathione Peroxidase 1

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) in obesity is very high. The role of adiponectin receptors in NAFLD progression remains still unclear. We speculate that changes in the hepatic expression levels of the two adiponectin receptors may be associated with the expression of oxidative stress-related genes. We studied 60 morbidly obese patients with NAFLD, who underwent liver biopsy at the time of bariatric surgery. We measured the hepatic messenger-RNA concentration of adiponectin receptors (ADIPOR1 and ADIPOR2), glutathione peroxidase 1 (GPx1), glutathione reductase (GRd) and inducible oxide nitric synthase. Additionally, biochemical parameters and oxidative stress markers were determined in blood samples. According to the Kleiner score, the patients were divided into two groups: group 1 (25 patients without steatohepatitis) and group 2 (25 patients with probable steatohepatitis and ten patients with steatohepatitis). The messenger-RNA concentration of all genes analysed in the study was higher among the patients in group 2. However, no differences in blood oxidative stress markers were observed. Strong correlations were found among the expression levels of ADIPOR1, ADIPOR2 and GPx1. The multivariate analysis showed that the only independent variable associated with NAFLD progression was the increase in GPx1 expression levels. NAFLD progression in morbid obesity is associated with increase in hepatic adiponectin receptor and oxidative stress-related genes. The linear correlations suggest that ADIPOR1, ADIPOR2 and GPx1 share key molecular factors in the regulation of the genetic expressions.