Impact of high-fat diet on liver genes expression profiles in mice model of nonalcoholic fatty liver disease

- HFD feeding caused genes correlated to lipid metabolism and inflammatory up-regulated.
- HFD feeding caused genes related to oxidative stress and oxidoreduction elevated.
- HFD feeding caused genes involved in nucleic acid metabolism repressed.
- Genes involved in drug metabolism had 16 down-regulated and 21 up-regulated in NAFLD.
- HFD-induced DMEs alterations may result in adverse reaction or drug toxicity in NAFLD.

Evidences have shown that NAFLD influences expression of some drug metabolic enzyme genes. This study aims to investigate the role of HFD-induced NAFLD in regulating the transcription of genes, particularly the drug metabolizing genes variation. Transcriptome analysis demonstrated that HFD feeding caused the 150 genes expression to change, most genes associated with lipid metabolism, inflammatory, oxidative stress and oxidoreductase activity up-regulated, whereas most genes involved in nucleic acid metabolism repressed. The genes involved in drug metabolism had 16 down-regulated and 21 up-regulated in NAFLD. The over-4-fold change genes included the down-regulation of Cyp8b1, Cyp7a1, Sult3a1, Sult1e1, Cyp17a1, Cyp3a41a, Gstt3, Cyp51, Cyp2c54 and Cyp4f14, and the up-regulation of Asns, Past1, Cyp2c55, Gstm2, Cyp2e1 and Gstaα1. In conclusion, significant alterations in the expression of drug metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions or drug toxicity in nonalcoholic fatty liver disease.