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

Abstract

Background/aim: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: CMKLR1; Liver tumor; NASH; chemerin activity.