FGF21对NEFA介导肝脂质沉积及AMPK调控因子的影响特征

研究旨在阐明成纤维细胞生长因子21（FGF21）对AMPK磷酸化调控因子的影响机制,并明确FGF21对高NEFA介导的小鼠肝细胞脂滴代谢的影响特征。对AML12小鼠肝细胞进行添加NEFA和（或）沉默FGF21处理,应用荧光定量PCR技术检测肝细胞FGF21、肝激酶B1（LKB1）、转化生长因子β激活激酶1（TAK1）、钙调蛋白依赖性蛋白激酶（CaMKK）mRNA表达水平;用油红O染色检测肝脂沉积水平。结果显示,沉默FGF21,显著（P<0.05）降低LKB1表达,而对TAK1、CaMKK表达量没有显著（P>0.05）影响。高浓度NEFA下,沉默FGF21肝细胞脂质沉积水平显著增高。由该试验结果可以得出,高NEFA下肝细胞FGF21可能通过诱导LKB1激活AMPK信号通路,进而减少肝细胞脂质沉积。

Effects of FGF21 on NEFA-mediated Hepatic Lipid Deposition and AMPK Regulatory Factors

Abstract：The purposes of this study were to elucidate the underlying mechanism responsible for the impact of fibroblast growth factor 21 （FGF21） on AMPK phosphorylation regulatory factors, and to clarify the effect of FGF21 on lipid droplet metabolism mediated by high NEFA in mouse hepatocytes. The AML12 mouse hepatocytes were received the treatment of NEFA addition and （or） FGF21 gene silencing; after that, the mRNA expression levels of FGF21, hepatokinase B1 （LKB1）, transforming growth factor β-activated kinase 1 （TAK1）, and calcium/calmodulin-dependent protein kinase kinase（CaMKK） of the mouse hepatocytes were assessed by using fluorescence quantitative PCR assay; the level of hepatic lipid deposition was detected by oil red O staining. The results showed that silencing of FGF21 gene significantly （P<; 0.05） decreased the mRNA expression level of LKB1, but had no significant effect on the mRNA expression level of TAK1 and CaMKK （P>; 0.05）. Furthermore, the level of lipid deposition in hepatocytes was significantly （P<; 0.05） elevated after silencing of FGF21 gene under high NEFA. In conclusion, FGF 21 may reduce the lipid deposition in mouse hepatocytes under high NEFA by activating AMPK signaling pathway via inducing LKB1.