Identification of Chemerin as a Novel FXR Target Gene Down-Regulated in the Progression of Nonalcoholic Steatohepatitis

Chemerin is an adipokine involved in obesity, inflammation, and innate immune system that is highly expressed in the liver. In the present study, we find that chemerin mRNA expression is decreased in the livers of rodents with nonalcoholic fatty liver disease as well as in HepG2 cells after lipid overloading. Moreover, we report that chemerin expression and secretion are induced in HepG2 cells and primary hepatocytes from wild-type mice, but not farnesoid X receptor (FXR)-/- mice, in response to the synthetic FXR ligand GW4064. Hepatic chemerin expression is decreased in FXR-/- mice but up-regulated by GW4064 administration in wild-type mice. Dual-luciferase reporter assay and chromatin immunoprecipitation analyses further identified a functional FXR response element located in the -258-bp /+ 121-bp region of the chemerin gene. These data demonstrate that chemerin, a novel target gene of FXR, is related to nonalcoholic steatohepatitis. (Endocrinology 154: 1794-1801, 2013)