Study On The Mechanism Of The Regulating The Metabolism Of HepG2 By Wnt/β-catenin Signaling Pathway

Background Since the beginning of the 21 st century,the development of the social economy has become increasing rapidly,and people’s lifestyles are undergoing tremendous changes,accompanied with these tremendous changes.The incidence of metabolic-related diseases such as type II diabetes,obesity,hyperlipidemia,and non-alcoholic fatty liver is increasing.Liver is the most important digestive and metabolic organ,and many metabolic diseases are inextricably linked with the liver.And the metabolism of liver depends on the metabolism of hepatocytes,the metabolism of hepatocytes is regulated by many mechanisms.Wnt / β-catenin signaling plays an important regulatory role in the homeostasis and metabolism of liver,but its specific mechanism is still unclear.Therefore,to reveal the metabolism of how the Wnt / β-catenin signaling pathway regulates the liver cell is of great significance.Objective The reaseach is to verify the regulatory effect of Wnt/β-catenin signaling pathway on Hep G2 cells and elucidate its regulatory mechanism through experimental studies.Methods The Wnt / β-catenin signaling pathway of Hep G2 cells was activated by the activator of Wnt / β-catenin signaling pathway,and the changes of Wnt / β-catenin signaling pathway target genes(TCF1,c-jun and others)were detected by RT-PCR.The changes of genes(FGF21,PPARγ,SCD1,etc.),proteins(FGF21,IRS1,P-IRS1,P-IRS1 and P-IRS1,AKT,etc.)related with metabolism were detected by RT-PCR,Western Blot and ELISA.And the changes in cell aerobic respiration(OCR)and glycolysis capacity(ECAR)were detected by seahorse cell energy metabolizer.Then by using RT-PCR and Western Blot for further pathway screening.Results 1.Compared with control group,after the activation of Wnt / β-catenin signaling pathway,Wnt / β-catenin signaling pathway genes such as Cyclin D1,TCF1,c-jun of Hep G2 cells have increased significantly;2.Compared with control group,after the activation of Wnt / β-catenin signaling pathway,the genes related with metabolism such as FGF21、PPARγ、SCD1 of Hep G2 cells have changed a lot;3.Compared with control group,after the activation of Wnt / β-catenin signaling pathway,there’s a certain change of the proteins related with metabolism such as FGF21、IRS1、P-IRS1、P-AKT of Hep G2 cells;4.Compared with control group,after the activation of Wnt / β-catenin signaling pathway,there is no significant change in cell aerobic respiration(OCR)and glycolysis(ECAR)capacity of Hep G2 cells;5.Through the pathway screening,it was found that the ER stress pathway changed greatly after the Wnt / β-catenin signaling pathway was activated.Conclusions 1.After the activation of Wnt / β-catenin signaling pathway,there is a significant change in metabolism of Hep G2 cells,indicating Wnt / β-catenin signaling pathway has an important regulatory role on the metabolism of Hep G2 cell;2.Wnt / β-catenin signaling pathway may regulate the metabolism of Hep G2 cells through the ERS(endoplasmic reticulum stress)pathway.