Differential effects of medium- and long-term high-fat diets on the expression of genes or proteins related to nonalcoholic fatty liver disease in mice

Abstract

Non-alcoholic fatty liver disease (NAFLD) is now considered to be the most common liver disease worldwide, caused by fat deposition in hepatocytes. High-fat diet is considered to be a major lifestyle factor predisposing to NAFLD. However, the effect of different cycles of high-fat diets on changes in NAFLD-related gene and protein expression is unclear. In this study, NAFLD mouse models were established by feeding C57BL/6 male mice a high-fat diet for 16 and 38 weeks. The transcriptome and proteome of mouse liver were profiled by RNA sequencing and high-resolution mass spectrometry, respectively. The results show that accumulation of liver lipids was observed at 38 weeks of treatment on a high-fat diet. At the same time, the expression profiles of 1329 genes and 802 proteins involved in NAFLD were changed, with a total of 234 genes and 37 proteins significantly changing by more than twice. These differentially expressed genes and proteins were significantly enriched in fatty acid metabolism and organic acid biosynthesis. 18 genes and their corresponding protein overlaps were identified using Venn diagrams, and most of them were regulated by high-fat diet in an aging-dependent manner. All in all, our study is valuable for understanding the high-fat diet on the developmental process of NAFLD.