Elevated Irisin Expression in NASH Livers

Abstract

BackgroundData mining with our microarray database suggested that irisin is one of the most highly elevated genes in livers of non‐alcoholic steatohepatitis (NASH). NASH is the severe form of non‐alcoholic fatty liver disease (NAFLD) and is characterized by hepatic steatosis, inflammation and fibrosis. Irisin, an adipomyokine implicated in the initiation of a browning effect of adipose that may profoundly affect the metabolic status of NASH patients. Our microarray analysis suggested elevated liver irisin and chemokine ligand 14 (CXCL14). CXCL14 is a chemokine that participates in glucose metabolism and inflammation. We therefore tested the hypothesis that inflammation is a trigger for hepatic irisin expression.MethodsBiopsy‐proven adolescent NASH patients were compared to controls from healthy livers from donors of similar age and gender. Irisin gene expression was evaluated by microarray and quantitative real‐time PCR.ResultsHepatic irisin gene expression was increased in NASH compared to controls. Microarray data showed NASH/Normal = 30.49(p = 0.0008) and CXCL14/Normal = 108.34 (p = 0.0005). qRT‐PCR showed elevated irisin (p =0.0001) and CXCL14 (p=0.0009) expression. Significant correlations were noted between irisin message and hepatic inflammation grade (r = ‐ 0.65, p = 0.0008) but not the pathologic scores for fibrosis or steatosis.ConclusionsThis study indicates that irisin gene expression is induced in NASH. Irisin expression correlates with CXCL14, a representative inflammatory chemokine. These observations suggest that irisin may be playing a role in the mechanism of inflammation.