Effect Of High-fat Diet On Oxidative Stress And Lipid Metabolism Related Gene Expression Of Mice

This investigation was conducted to evaluate the effect of high-fat diet on the oxidative stress of digestive system, blood lipid metabolism and the coherent gene expression of mice. The experiment was also carried out to determine the effect of lipoic acid (LA) on the scavenging of free radical and the regulating of blood lipid metabolism of mice fed with high-fat diet. This research contributes to the pathology mechanism of cardio-cerebral vascular diseases. It also Provide the theoretical basis for LA as an antioxidant nutrients.Method: 40 Kunming mice were randomly divided into 4 groups. Mice were administrated by gastric perfusion of saline, lard, lard+0.05%LA and lard+0.1%LA 0.2mL respectively after food intake. The level of free radical in blood of mice was determined at 0 h, 0.5 h, 1.0 h, 1.5 h, 2.0 and 2.5h after intragastric administration.Another 40 mice were randomly grouped to four groups, The control group was fed with basal diet and another three groups were fed with high-fat diet, high-fat diet plus 0.05% LA and high-fat diet plus 0.1%LA respectively. After 6 weeks,the mice's blood and gastrointestinal organ level of free radical,antioxidation index,the level of triglyceride(TG), total cholesterol(TC),high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in blood plasma and liver were examined. The activity of lipoprotein lipase (LPL) and hepatic lipase (HL) in blood plasma were also determined respectively. In addition, in order to explore the molecular mechanisms underlying the modulating effect of LA on high-fat diet induced dyslipidemia, the expression of Carnitine palmitoyltransferase-1a (Cpt1a) and Apolipoprotein E (ApoE) were examined by real-time reverse transcription–polymerase chain reaction. The results were shown as follows: Intragastricing lard can significantly increase the level of free radical in blood of mice compared to controls.Adding 0.1%LA to lard can significantly decrease the level of free radical.The level of free radical produced in blood, liver, pancreas, stomach, duodenum, jejunum and ileum were significantly increased by feeding high-fat diet as compared to the controls. The antioxidation index of mice in high-fat diet groups were significantly decreased as compared to controls. The high-fat diet disturbed blood lipid metabolism in mice. The activities of LPL and HL of mice were significantly decreased by feeding them with high-fat diet as compared to controls. The expression of Cpt1a in liver was significantly lowered in mice fed with high-fat diet and ApoE in liver was significantly increased in mice fed with high-fat diet as compared to the controls.The levels of free radical in digestive system and the antioxidation index of mice were recovered approaching to the controls when 0.1%LA was added. But addition of 0.05%LA in the high-fat diet fails to scavenge free radical and increase the antioxidation index of mice.The blood lipid metabolism, the activity of LPL and HL in blood plasma and the gene expression of Cpt1a and ApoE of mice fed with high-fat diet could be modulated approaching to the controls when 0.1%LA were added, meanwhile addition of 0.05%LA in the high-fat diet fails to adjust the blood lipid metabolism and the gene expression.Conclusion: High-fat diet resulted in oxidative stress in digestive system and disturbed the blood lipid metabolism of mice. The optimum dose of LA could be able to eliminate free radical, increase the antioxidative capacity, adjust the blood lipid metabolism and the expression of Cpt1a and ApoE in liver of mice fed with high-fat diet.