Expression profile of hepatic cytochrome 450 proteins in high fat and high fructose fed mice

Abstract

Introduction: Cytochrome P450 (CYP) is a superfamily of drug metabolized enzymes mainly located in the liver that plays an important role in catalyzing biotransformation of endogenous compounds and other substances such as drugs and environmental chemicals. The fast-paced life adapts people dietary habit to fast food with full of  high fat and high fructose, which is one factor implicating metabolic disorders and can cause hepatic pathology such as non-alcoholic fatty liver disease. This pathology of liver results in modification of hepatic metabolism function. Therefore, the present study aims to investigate the expression profile of hepatic CYP450 protein of high fat- and high fructose-fed mice. Materials and Method: Seven-week-old male ICR mice (n=5) were intragastrically given 65% hydrogenated soil bean oil 1 mL/day/mouse and freely accessed to 20% fructose in drinking water daily for 2, 4, or 8 weeks while the regular diet-fed mice (n=5) were employed as a control in this study. The mice were sacrificed at 24 h after the last treatment and the hepatic microsome was prepared. The animal handling was approved by the Animal Ethics Committee for Use and Care of Khon Kaen University, Thailand (Approval No. AEKKU 92/2555). The expression of CYPs protein including CYP1A1/2, CYP2B9/10, CYP1B1, and CYP3A11 were performed using Western blotting analysis technique followed by statistically analyzed by ANOVA and tukey’s post hoc test. Results: In high fat- and high fructose-fed mice, there was no significantly change of hepatic CYP1A1/2 protein expression profile compared to the mice fed with regular diet, while the protein expression levels of CYP2B9/10 was reduced significantly after administration of high fat and high fructose diet for 4 and 8 weeks. The significant increase of CYP1B1 protein expression was observed after 8 weeks of the treatment while that of CYP3A11 protein was elevated after the 4- to 8-week treatment. These observations supported that continuous consuming of the high fat- and high fructose dietary could modify the expression levels of hepatic CYP450 proteins. Conclusion: Alteration of the expression profiles of hepatic CYP2B9/10, CYP1B1, and CYP3A11 proteins was significantly related to the duration of high fat- and high fructose-intake. The change of CYP activity may possibly affect drug or xenobiotic metabolism which can lead to ineffective treatment or increasing risk of toxicity. These findings suggested the high-fat high-fructose-fed mice as a useful animal model for studying metabolic condition via regulation of CYP enzyme that related to drug metabolism or drug interaction.