The Role And Mechanism Of Vitamin D In Nonalcoholic Fatty Liver Disease

Backgrounds:Nonalcoholic fatty liver disease（NAFLD）is a disease in which lipids are abnormally deposited in hepatocytes.Underlying pathogenesis is complicated.Epidemiological studies suggest a link between vitamin D deficiency and increased risk of nonalcoholic fatty liver disease（NAFLD）in patients.However,the specific regulatory mechanisms are not clear,and related basic research is lacking.This study aimed to explore the regulatory role and mechanism of vitamin D and its receptor（VDR）in the progression NAFLD.Methods and materials:Palmitic acid（PA）treated normal human hepatocytes cell line L02 was used to construct a cell model.C57BL/6 mice were fed a high fat diet（HFD）to to establish a cellular model of NAFLD.Vitamin D was added to mouse diet and hepatocyte-specific VDR knockout C57BL/6 mice were used to investigate the effects of vitamin D and VDR on NAFLD.In vitro study,1.25（OH）₂VD₃ and VDR si RNA were used to explore the effect of vitamin D and VDR on NAFLD.Hematoxylin-Eosin（H&E）staining,Oil Red O staining,liver triglyceride（TG）measurement,blood glucose measurement,glucose and insulin tolerance test,Western blot（WB）,Immunofluorescence（IF）,co-Immunoprecipitation（co-IP）studies were used to investigate the effects and underlying mechanisms.Research result:Vitamin D supplementation to HFD-fed mice can significantly reduce hepatic steatosis and insulin resistance.Liver VDR expression was induced in HFD-fed mice.Hepatic-specific VDR knockout mice aggravated hepatic steatosis and insulin resistance after HFD compared with Flox control mice.However,vitamin D could not reduce hepatic steatosis and insulin resistance in HFD-induced VDR knockout mice.In vitro study,vitamin D supplementation could reduce PA-induced hepatic accumulation of lipid,while knocking down VDR aggravated PA-induced hepatic accumulation of lipid.Further mechanistic studies have found that VDR regulated NAFLD through the interaction with hepatocyte nuclear factor 4α（HNF4α）,a transcription factor related to TG export,thereby reduding TG in hepatocytes.Analysis conclusion:Our study found vitamin D ameliorates NAFLD via the activation of hepatic VDR and interaction with HNF4α.The role of vitamin D and VDR in NAFLD provided new evidence for the diagnosis and treatment of NAFLD.