title: FGF21 treatment ameliorates alcoholic fatty liver through activation of AMPK-SIRT1 pathway.
abstract: Fibroblast growth factor 21 (FGF21), a recently identified member of the FGF superfamily, is mainly secreted from the liver and adipose tissues and plays an important role in improving metabolic syndrome and homeostasis. The aim of this study is to evaluate the role of FGF21 in alcoholic fatty liver disease (AFLD) and to determine if it has a therapeutic effect on AFLD. In this paper, we tested the effect of FGF21 on alcohol-induced liver injury in a murine model of chronic ethanol gavage and alcohol-treated HepG2 cells. Male KM mice received single dose of 5 g/kg ethanol gavage every day for 6 weeks, which induced significant fatty liver and liver injury. The alcohol-induced fatty liver cell model was achieved by adding ethanol into the medium of HepG2 cell cultures at a final concentration of 75 mM for 9 days. Results showed that treatment with recombinant FGF21 ameliorated alcoholic fatty liver and liver injury both in a murine model of chronic ethanol gavage and alcohol-treated HepG2 cells. In addition, FGF21 treatment down-regulated the hepatic expression of fatty acid synthetic key enzyme, activated hepatic AMPK-SIRT1 pathway and significantly down-regulated hepatic oxidative stress protein. Taken together, FGF21 corrects multiple metabolic parameters of AFLD in vitro and in vivo by activation of the AMPK-SIRT1 pathway.
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China School of Food Science and Technology, State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Shenglong
authors.initials: S
authors.lastname: Zhu
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China.
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China.
authors.forename: Xianlong
authors.initials: X
authors.lastname: Ye
authors.affiliation: China Agricultural University, Beijing 10008, China.
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China.
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China School of Life Science, University of Baghdad, 999048, Iraq.
authors.forename: Lubna Muhi
authors.initials: LM
authors.lastname: Rasoul
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China.
authors.forename: Yunye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Guo
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China deshanli@163.com renguiping@126.com.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin 150001, China Key Laboratory of Agricultural Biological Function Gene, Northease Agricultural University, Harbin 150001, China deshanli@163.com renguiping@126.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001823:Body Composition / Q000187:drug effects; D045744:Cell Line, Tumor; D017931:DNA Primers; D004789:Enzyme Activation; D005235:Fatty Liver, Alcoholic / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D005247:Feeding Behavior / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D008055:Lipids; D017382:Reactive Oxygen Species; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D000263:Adenylate Kinase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: AMPK; SIRT1; alcoholic fatty liver; fibroblast growth factor 21 (FGF21)