Effect of FKBP38 expression on occurrence and development of nonalcoholic fatty liver disease in mice / 中国药理学通报

ABSTRACT

Aim To investigate the effects of FKBP38 gene on nonalcoholic fatty liver disease ( NAFLD ) model induced by methionine and choline deficiency j J diet (MCD) in mice.Methods The mutant model of hepatocellular specific deletion of FKBP38 gene was successfully established.The mice were divided into wild-type group ( WT) and homologous knockout group (L-FKBP38 ).Mice were fed with MCD for four weeks to construct NAFLD model.Liver injury was e- valuated by the contents of alanine transaminase (ALT), aspartate transaminase (AST) in the serum samples.We also performed HE staining, examined lipid accumulation by triglyceride (TG) and total cholesterol (CHO) and oil red staining, as well as macrophage infiltration by F4/80 immunohistochemical stai-ning of the liver sections.Fatty acid metabolism-relat ed genes were quantifier] by Quantitative Real-time PCR assays.Results Comparer] with WT group, the levels of ALT, AST, TG and CHO in serum signifi- eantly inereased ( P < 0.05 ) ; liver damage , lipid ac- eumulation, and maerophage infiltration were markedly more severe, and the expressions of fatty aeirl oxidation related genes PPARa, ACOX-1 , CPT-la and SIRT3 markedly rleereaserl ( P < 0.05) in the liver samples of L-FKBP38 group.Conclusions Hepatocellular speeifie deletion of FKBP38 intensifies lipid accumula- tion by inhibiting fatty aeid oxidation in the liver, thus exaeerbating nonaleoholie fatty liver disease.