Diet-induced non-alcoholic fatty liver disease affects expression of major cytochrome P450 genes in a mouse model

Abstract

Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with impaired liver function, and resveratrol could suppress NAFLD progression. This study examined the effects of NAFLD on the expression of major cytochrome P450 (CYP) subtypes in the liver and whether the expression could be attenuated by resveratrol.

Methods: C57BL/6 mice (male, 10 weeks of age) were fed a high-fat and high-sucrose (HFHS) diet to induce NAFLD. Major Cyp subtype mRNA expression in the liver was measured by real-time RT-PCR.

Key findings: Body and liver weights at 4 and 12 weeks were significantly higher in mice fed the HFHS diet compared with control. The HFHS diet significantly increased the accumulation of cholesterol and triglycerides at 12 weeks. Under this condition, the HFHS diet increased the expression of Cyp1a2 and decreased that of Cyp3a11 at 1 week and thereafter. On the other hand, Cyp1a1, 2b10 and 2c29 mRNA expression levels in the liver were significantly increased at 12 weeks only. Resveratrol (0.05% (w/w) in diet) slightly suppressed lipid accumulation in the liver, but failed to recover impaired Cyp gene expression levels in NAFLD.

Conclusions: Drug metabolism may be impaired in NAFLD, and each Cyp subtype is regulated in a different manner.

Keywords: Cyp; cytochrome P450; non-alcoholic fatty liver disease; resveratrol.