Vitamin D Improves the Lipotoxicity of Liver Cells by Adjusting Epigenetic Characteristics of Genes

Background: With the improvement in living standards and the change in eating habits, the prevalence of nonalcoholic fatty liver disease (NAFLD) has gradually increased, and it has become one of the most common chronic liver diseases worldwide. Objectives: In this study, we used vitamin D3 to interfere with the hyperlipidemia-induced NAFLD cell model to explore the mechanism of vitamin D in improving the lipotoxicity of liver cells by regulating the epigenetic characteristics of genes and to provide new clues for the treatment of late-stage NAFLD. Methods: GSE200765, a data chip for vitamin D3 intervention in liver cell lipotoxicity, was screened from the GEO database. They were divided into the control group (untreated), model group (oleic OA/PA), and vitamin D3 intervention group (OA/PA+SV-VD3 group). Differential expression genes between the control group and model group, model group, and vitamin D3 intervention group were screened by the GEO2R tool. Differentially expressed genes construct a target PPI network map through the STRING database and analyze the KEGG pathway of differentially expressed genes in the DAVID database. The t-test or Unpaired t-test with Welch's correction was used to analyze the expression trend of pathway genes. Results: Compared with the control group, 218 genes were up-regulated, and 255 genes were down-regulated in the model group, of which 26 genes were enriched in the complex and coagulation cascades and cell cycle pathways. After oleic OA/PA was added to HepaRG cells, the complex and coordination cascades pathway was relatively weak, and the cell cycle pathway was relatively strong. Compared with the model group, 554 genes were up-regulated, and 704 genes were down-regulated in the vitamin D3 intervention group, of which 23 genes were enriched in the apoptosis pathway. The apoptosis pathway was relatively weakened after vitamin D3 intervened in oleic OA/PA-treated HepaRG cells. The trend analysis of gene expression in the pathway showed that gene expression disorder in the complex and coagulation cascades, cell cycle, and apoptosis pathways were reversed after vitamin D3 intervention. Conclusions: Through bioinformatics, key pathway genes of vitamin D intervention on hepatocyte lipotoxicity were discovered, which were related to the complex and coordination cascades, cell cycles, and apoptosis pathways. The inhibition of vitamin D on lipotoxicity of human hepatocytes and the possible reversal mechanism was found, which provided ideas for the later treatment of NAFLD and hepatocyte damage.