The Role Of FGF21 In Diabetes Mellitus-induced NASH And Its Mechanism

Fibroblast growth factor 21(FGF21)concentrations are increased in human subjects who either have type 2 diabetes or nonalcoholic fatty liver disease(NAFLD).While excessive fat in the liver promotes the release of pro-inflammatory cytokines,NAFLD progresses from simple steatosis to non alcoholic steatohepatitis(NASH),a more aggressive form of hepatic damage,and lastly toward cirrhosis and HCC.In this study,we proposed to investigate the liver metabolic disorders by diabetes and the potential roles of FGF21 played in NASH and potential carcinogenetic transformation of HCC.FGF21 knockout(FGF21KO)mice was used to induce NASH by diabetes or fed with high fat diet(HFD).The pathological transformation of steatohepatities as well as parameters of inflammation,lipid metabolism,cellular events,mesenchymal–epithelial transition(MET)and Wnt/β-catenin signaling was determined in the FGF21 KO diabetic mice and HFD fed mice.We found that mice lacking the FGF21 gene are more prone to develop NASH.A compromised microenvironment of NASH,which could facilitate the HCC carcinogenetic transformation,was found in FGF21 KO mice under metabolic disorders by diabetes and HFD feeding.This study provided further evidence that lack of FGF21 worsened the metabolic disorders in NASH and could render a compromised microenvironment in the liver.