Transcriptome analysis reveals ameliorated liver steatosis along with metabolism and inflammation remodeling in high-fat diet induced NAFLD mice after polyene phosphatidylcholine intervention

Recent years have witnessed a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling with the global outbreak of obesity. NAFLD is often associated with significant complications such as liver cirrhosis and hepatocellular carcinoma, which makes it a formidable disease. However, the pathogenesis of NAFLD requires more analysis. This study aimed to elucidate the effect and mechanism of classic hepatoprotective drug polyene phosphatidylcholine (PPC) on NAFLD. The results showed PPC intervention lowered the body weight, reduced the mass of liver, subcutaneous, epididymal and brown fats in high-fat diet (HFD) mice. Furthermore, PPC supplementation reversed the high serum level of triglyceride (TG), low density lipoprotein (LDL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) induced by HFD. PPC supplementation also mitigated liver steatosis and improved insulin sensitivity. Using transcriptome analysis, there were 1789 differentially expressed genes including 893 upregulated genes and 896 downregulated genes in the HFD group compared to LC group. 114 upregulated genes and 1337 downregulated genes in HFD+PPC group were identified in comparison to HFD group. With the help of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, the study found that lipoglysis, fatty acid oxidation and lipid export were upregulated while uptake of lipids and cholesterol synthesis were downregulated in liver after PPC supplementation. Interestingly, PPC attenuated the metabolic inflammation via inhibiting M1 macrophage polarization in the liver of mice fed by HFD. The complex metabolic remodeling and macrophage polarization after PPC supplementation may be accountable for the improvement of NAFLD. Overall, this study suggested that PPC could ameliorate the HFD-induced NAFLD. Thus, our findings provide novel clues to emerge targets for drug development of NAFLD.