title: Identification of chemerin as a novel FXR target gene down-regulated in the progression of nonalcoholic steatohepatitis.
abstract: 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.
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, 197 Ruijin Road II, Shanghai 200025, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Deng
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Rongfeng
authors.initials: R
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Weili
authors.initials: W
authors.lastname: Shen
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D007555:Isoxazoles; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C478630:RARRES2 protein, human; C412815:GW 4064