This study is aimed at evaluating the effects, functions, and mechanism of HNF1á on hepatic glycolipid metabolism. In this study, free fatty acid- (FFA-) induced steatosis of hepatocyte liver cell LO2 was used as an in vitro model. The methods of Oil Red O staining, RT-qPCR, western blot, and immunofluorescence staining were used to detect LO2-regulated HNF1á expression and its effects on FFA-induced LO2 cell steatosis, the insulin signaling and SOCS-3-STAT3 signaling pathways, the expression of lipid metabolism-related regulators, and phosphorylation. With increased FFA induction time, the expression of HNF1á in the LO2 fatty degeneration hepatic cells gradually decreased. Downregulation of HNF1á expression aggravated FFA-induced steatosis of LO2 hepatocytes. HNF1á promotes activation of the insulin pathway and oxidative breakdown of fat and inhibits lipid anabolism. Inhibitors of STAT3 can reverse the regulation of decreased HNF1á expression on the insulin signaling pathway and fat metabolism. We also confirmed this pathway using HNF1á-/- mice combining treatment with STAT3 inhibitor NSC 74859 in vivo. HNF1á regulates hepatic lipid metabolism by promoting the expression of SOCS-3 and negatively regulating the STAT3 signaling pathway.
Animals Gene Expression Regulation