Elevated hepatic chemerin mRNA expression in human non-alcoholic fatty liver disease

Objective: Adipose tissue- derived factors link non-alcoholic fatty liver disease (NAFLD) with obesity, which has also been reported for circulating chemerin. On the other hand, hepatic chemerin and chemokine- like receptor 1 (CMKLR1) mRNA expression has not yet been studied in an extensively characterized patient collective. Design: This study was cross-sectional and experimental in design. Methods: Liver tissue samples were harvested from 47 subjects and histologically examined according to the NAFLD activity score (NAS). The concentrations of chemerin and CMKLR1 were measured using semi-quantitative real-time PCR, and the concentration of serum chemerin was measured using ELISA. To evaluate potential effects of chemerin and CMKLR1, cultured primary human hepatocytes (PHHs) were exposed to selected metabolites known to play a role in NAFLD (insulin, glucagon, palmitoic acid, and interleukin-6 (IL6)). Results: Chemerin and CMKLR1 mRNA levels were elevated in the human liver. Their expression was correlated with the NAS ( R-2=0.543; P<0.001 and R-2=0.355; P<0.014 respectively) and was significantly elevated in patients with definite non- alcoholic steatohepatitis (NASH) (P<0.05 respectively). Linear regression analysis confirmed an independent association of liver fibrosis, steatosis, inflammation, and hepatocyte ballooning with hepatic chemerin mRNA expression (P<0.05 respectively). The expression of hepatic chemerin and CMKLR1 was correlated with the measures of obesity (P<0.05). The incubation of PHHs with IL6 significantly increased the expression of CMKLR1 mRNA (PZ0.027), while that of chemerin remained unaffected (PO0.05). None of the other metabolites showed an influence (PO0.05). Conclusion: This is the first study to show that chemerin mRNA expression is significantly elevated in the liver of NASH patients and that CMKLR1 expression is upregulated in liver inflammation, whereby IL6 could play a causal role.