Zhu Shenglong, Ma Lei, Wu Yunzhou, Ye Xianlong, Zhang Tianyuan, Zhang Qingyang, Rasoul Lubna Muhi, Liu Yunye, Guo Mo, Zhou Bing, Ren Guiping, Li Deshan
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.
School of Life Science, Northeast Agricultural University, Harbin 150001, China Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China.
Acta Biochim Biophys Sin (Shanghai). 2014 Dec;46(12):1041-8. doi: 10.1093/abbs/gmu097. Epub 2014 Oct 29.
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.
成纤维细胞生长因子21（FGF21）是FGF超家族中最近发现的成员，主要由肝脏和脂肪组织分泌，在改善代谢综合征和体内平衡方面发挥重要作用。本研究的目的是评估FGF21在酒精性脂肪肝病（AFLD）中的作用，并确定其对AFLD是否具有治疗作用。在本文中，我们在慢性乙醇灌胃小鼠模型和酒精处理的HepG2细胞中测试了FGF21对酒精诱导的肝损伤的影响。雄性KM小鼠每天接受单剂量5 g/kg乙醇灌胃，持续6周，这导致了明显的脂肪肝和肝损伤。通过在HepG2细胞培养基中加入终浓度为75 mM的乙醇9天，建立酒精诱导的脂肪肝细胞模型。结果表明，重组FGF21治疗可改善慢性乙醇灌胃小鼠模型和酒精处理的HepG2细胞中的酒精性脂肪肝和肝损伤。此外，FGF21治疗下调了脂肪酸合成关键酶的肝脏表达，激活了肝脏AMPK-SIRT1通路，并显著下调了肝脏氧化应激蛋白。综上所述，FGF21通过激活AMPK-SIRT1通路在体外和体内纠正了AFLD的多个代谢参数。
