Expression And Significance Of FTO And FoxO1in NAFLD

BACKGROUNDThe pathogenesis of non-alcoholic fatty liver disease (NAFLD) is complex andreferred to the interactions among hereditary、Environment、metabolism and stress. Itis also reported to be closely linked with obesity. Fat mass and obesity associated(FTO) gene was a new discovered gene related to obesity. FTO enhances theoxidative stress and lipogenesis in NAFLD. On the other hand, the forkheadtranscription factor O1(FoxO1) is another important genes, causing lipid disorderswhen insulin resistance appeared in liver. However, the interactions between FTOand FoxO1during the pathogenesis of NAFLD have not been fully elucidated. Thisstudy was designed to identify the relationship of these two factors, including theexpression levels and histological localization of FTO and FoxO1in mouse models ofNAFLD and hepatic steatosis. OBJECTIVEThe purpose of this article was to detect FTO, FoxO1and AMPK expressionlevel in liver of NAFLD and analyze the correlation between them further exploringthe molecular mechanism of NAFLD. To investigate the expression levels of FTOand FoxO1in human L02liver cells induced by fat, and to explore the specificmechanism in non-alcoholic fatty liver disease.METHODSFeeding mice with high-fat food to prepare for nonalcoholic fatty liver diseaseanimal model, detecting mice liver weight, weight calculation index;using fullyautomatic biochemical instrument to detect AST, ALT, TG, TC, ALP, HDL andLDL; Using HE staining method to detect mice liver pathology; Usingimmunohistochemical method to detect FTO protein, FoxO1protein, the expressionof AMPK and histological localization.50%fetal bovine serum medium was used toset model group. Both of the two group were trained for24h,48h,72h; Using Oilred O staining to observe intracellular lipid droplets;detecting liver enzymes such asALT,AST,ALP,LDH and TG levels by automatic biochemical;using RT-PCR toanalyzing FTO mRNA、 FoxO1mRNA.RESULTSAt the end of10weeks, liver weight, height, and weight&liver indexsignificantly increased in case group than control (P <0.01); ALP, ALT, AST, LDLsignificantly increased (P <0.01) the TC, TG significantly higher (P <0.05) and HDLsignificantly decreased (P <0.05); HE staining showed a massive fatty degenerationin hepatic lobule and manifold area associated with inflammatory cells infiltrationand some of the dot liver. Non steatosis was observed in control group; FTO proteinand FoxO1protein expression are poorly differentiated in control group. Both FTOand FoxO1expressed significantly higher (P <0.01) in case group than control andthe expression of the two factors are significantly correlated. AMPK in high-fat groupexpress lower with correlation with FTO but not FoxO1.Oil red O staining results showed that the cells were cultured by50%fetal bovine serum for24h,48h,72h,the cells become steatosis, ALT,AST,ALP,LDH,TG in model group were higher thanin normal control group and extended over time.FTO mRNA, FoxO1mRNAexpression obviously increased in model group than in the normal group (P <0.01);Expression levels of FTO mRNA, FoxO1mRNA are the highest at48h(P<0.05).CONCLUSIONSHigh fat leads to a higher expression of FTO, phosphorylated FoxO1anddecrease the AMPK phosphorylation. The interactions between FTO and FoxO1areclosely related to the pathogenesis of NAFLD.