FGF21 treatment ameliorates alcoholic fatty liver through activation of AMPK-SIRT1 pathway

Shenglong Zhu, Lei Ma, Yunzhou Wu, Xianlong Ye, Tianyuan Zhang, Qingyang Zhang, Lubna Muhi Rasoul, Yunye Liu, Mo Guo, Bing Zhou, Guiping Ren and Deshan Li

Acta Biochim Biophys Sin (Shanghai). 2014 Dec;46(12):1041-8. doi: 10.1093/abbs/gmu097

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

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 alcoholicfattyliver 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 fattyliver and liver injury. The alcohol-induced fattyliver 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 alcoholicfattyliver and liver injury both in a murine model of chronic ethanol gavage and alcohol-treated HepG2 cells. In addition, FGF21treatment down-regulated the hepatic expression of fatty acid synthetic key enzyme, activated hepatic AMPK-SIRT1pathway 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-SIRT1pathway.

图例: FGF21激活AMPK-SIRT1通路

全文: http://abbs.oxfordjournals.org/content/46/12/1041.full