Key result
A high-fat and choline-deficient diet induced early-stage non-alcoholic fatty liver disease in rats, resulting in 178 differentially expressed genes and 474 differentially expressed metabolites primarily related to lipid and cholesterol metabolism.
Why the study?
NAFLD can develop into NASH and liver cirrhosis, making the investigation of its formation and development mechanisms of great significance.
In an early rat model of NAFLD, a small number of genetic changes cause a strong response to lipid components, particularly glycerides and glycerophospholipids, indicating early characteristics of NASH.
Rat model data warrant no practice change; leaves open human validation of lipid pathways in early NAFLD.
Non-alcoholic fatty liver disease develops from simple steatosis to non-alcoholic steatohepatitis (NASH), which then potentially develops into liver cirrhosis. It is a serious threat to human health. Therefore, investigating the formation and development mechanism of non-alcoholic fatty liver disease (NAFLD) is of great significance. Herein, an early model of NAFLD was successfully established by feeding rats with a high-fat and choline-deficient diet. Liver tissue samples were obtained from rats in the fatty liver model group (NAFL) and normal diet control group (CON). Afterward, transcriptome and lipidomic analysis was performed. Transcriptome results revealed that 178 differentially expressed genes were detected in NAFL and CON groups. Out of which, 105 genes were up-regulated, 73 genes were downregulated, and 8 pathways were significantly enriched. A total of 982 metabolites were detected in lipidomic analysis. Out of which 474 metabolites were significantly different, 273 were up-regulated, 201 were downregulated, and 7 pathways were significantly enriched. Based on the joint analysis, 3 common enrichment pathways were found, including cholesterol metabolism and fat digestion and absorption metabolic pathways. Overall, in the early stage of NAFLD, a small number of genetic changes caused a strong response to lipid components. The strongest reflection was glycerides and glycerophospholipids. A significant increase in fatty acid uptake accompanied by cholesterol metabolism is the most prominent metabolic feature of the liver in the early stage of NAFLD. In the early stage of fatty liver, the liver had shown the characteristics of NASH.
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Zhai et al. (2021) studied Non-alcoholic fatty liver disease (n=14). High-fat and choline-deficient diet vs. Normal diet was evaluated on Differentially expressed genes and metabolites. A high-fat and choline-deficient diet induced early-stage non-alcoholic fatty liver disease in rats, resulting in 178 differentially expressed genes and 474 differentially expressed metabolites primarily related to lipid and cholesterol metabolism.
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