Chemerin in a Mouse Model of Non-alcoholic Steatohepatitis and Hepatocarcinogenesis.

Abstract

Non-alcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC). The adipokine chemerin protects from HCC and is reduced in human HCC. In this study, chemerin expression was analyzed in a murine model of NASH-HCC. Serum and hepatic chemerin, and ex vivo chemerin receptor activation were monitored in NASH and NASH-HCC in mice fed a low-methionine diet deficient in choline after initiation of tumors by injection of diethylnitrosamine. In non-tumorous liver tissues, the extent of hepatic steatosis, and the levels of proteins regulating hepatic lipids and liver fibrosis were similar in NASH and NASH-associated HCC. Systemic and hepatic chemerin, and chemerin receptor activation were not changed in HCC. Liver tumors only developed in diethylnitrosamine-injected mice and their number was increased in NASH. Chemerin protein was induced in liver in NASH, but was unchanged in HCC tissues. Hepatic and serum chemerin and ex vivo analyzed chemerin receptor activation do not differ in murine NASH-associated HCC when compared to NASH. Hepatic tumors still develop despite high endogenous levels of serum and liver chemerin protein.