The mechanism of dietary cholesterol effects on lipids metabolism in rats

Lipids in Health and Disease, Jan 2010

Background Cholesterol administration has been reported to influence hepatic lipid metabolism in rats. In the present study, the effect of dietary cholesterol on hepatic activity and mRNA expression of the enzymes involved in lipid metabolism were investigated. Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% cholesterol or cholesterol free AIN76 diets for 4 weeks. Results The serum triglyceride and high density lipoprotein cholesterol levels were significantly decreased but the total cholesterol and non high density lipoprotein cholesterol levels were significantly increased in the cholesterol-fed rats compared with the control rats. And the concentrations of the hepatic total cholesterol and triglyceride increased about 4-fold and 20-fold separately by dietary cholesterol. The activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, fatty acid synthase, phosphatidate phophatase and carnitine palmitoyl transferase were depressed by the cholesterol feeding (40%, 70%, 50%, 15% and 25% respectively). The results of mRNA expression showed that fatty acid synthase, carnitine palmitoyl transferase 1, carnitine palmitoyl transferase 2, and HMG-CoA reductase were down-regulated (35%, 30%, 50% and 25% respectively) and acyl-CoA: cholesterol acyltransferase and cholesterol 7α-hydroxylase were up regulated (1.6 and 6.5 folds) in liver by the cholesterol administration. Conclusions The dietary cholesterol increased the triglyceride accumulation in liver, but did not stimulate the activity and the gene expression of hepatic enzymes related to triglyceride and fatty acid biosynthesis.

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The mechanism of dietary cholesterol effects on lipids metabolism in rats

Lipids in Health and Disease The mechanism of dietary cholesterol effects on lipids metabolism in rats Yu-Ming Wang 0 Bei Zhang 0 Yong Xue 0 Zhao-Jie Li 0 Jing-Feng Wang 0 Chang-Hu Xue 0 Teruyoshi Yanagita 1 0 College of Food Science and Engineering, Ocean University of China , Qingdao , China 1 Department of Applied Biological Sciences, Saga University , Saga , Japan Background: Cholesterol administration has been reported to influence hepatic lipid metabolism in rats. In the present study, the effect of dietary cholesterol on hepatic activity and mRNA expression of the enzymes involved in lipid metabolism were investigated. Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% cholesterol or cholesterol free AIN76 diets for 4 weeks. Results: The serum triglyceride and high density lipoprotein cholesterol levels were significantly decreased but the total cholesterol and non high density lipoprotein cholesterol levels were significantly increased in the cholesterolfed rats compared with the control rats. And the concentrations of the hepatic total cholesterol and triglyceride increased about 4-fold and 20-fold separately by dietary cholesterol. The activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, fatty acid synthase, phosphatidate phophatase and carnitine palmitoyl transferase were depressed by the cholesterol feeding (40%, 70%, 50%, 15% and 25% respectively). The results of mRNA expression showed that fatty acid synthase, carnitine palmitoyl transferase 1, carnitine palmitoyl transferase 2, and HMG-CoA reductase were down-regulated (35%, 30%, 50% and 25% respectively) and acyl-CoA: cholesterol acyltransferase and cholesterol 7a-hydroxylase were up regulated (1.6 and 6.5 folds) in liver by the cholesterol administration. Conclusions: The dietary cholesterol increased the triglyceride accumulation in liver, but did not stimulate the activity and the gene expression of hepatic enzymes related to triglyceride and fatty acid biosynthesis. - Background The high dietary cholesterol was concerned with the increasing concentrations of serum and hepatic total cholesterol(TC), especially the level of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in serum, which is considered to be a primary risk factor of cardiovascular disease. Hypercholesterolemia rat model is represented for cardiovascular and cerebrovascular disease research, which can be established by feeding with 0.5%-1.0% cholesterol-supplement diet for several weeks. Dietary 0.5%-1.0% cholesterol can increase serum VLDL and LDL levels dramatically in rats. In this case, dietary cholesterol remarkably disturbed triglyceride (TG) metabolism, the hepatic TG content increased in folds until hepatic steatosis forms. Thereby, it has been developed as a non-alcoholic fatty liver disease (NAFLD) model induced by diet in some previous studies. However, the mechanism of the rat hypercholesterolemia and NAFLD by high dietary cholesterol has not been systematically investigated. Numerous studies have been done to seek the effect of dietary cholesterol on hepatic lipid homeostasis. In early 1990s, Thomas et al. [1,2] has investigated the effect of cholesterol on the accumulation of liver lipids through the radioisotope 14C-fatty acid and proposed that the hepatic TG accumulation was developed by the enhancement of hepatic TG synthesis and the reduction of fatty acid beta-oxidation. Liu et al. [3] has suggested the roles of increased lipogenesis, decreased oxidation of fatty acids and decreased secretion of VLDL as causes for the accumulation of TG in the liver in the cholesterol-fed rats. Xu et al. [4] has also reported that the impaired hepatic lipid homeostasis because of lipid accumulation attributed to the increasing activity of the enzymes involved in fatty acid biosynthesis in the rats by the dietary cholesterol. But in our study, we found that the activity of the enzymes correlated to lipogensis capacity did not increase by the dietary cholesterol. Besides, some researchers [5] thought the cholesterol synthesis was abolished in the high-cholesterol-fed rats, while we suggested the cholesterol administration affected not only the cholesterol catabolism but also the cholesterol biosynthesis. So the mechanism of dietary cholesterol on lipid metabolism is still unclear. As we know, VLDL is assembled in liver and secreted to serum, and high hepatic TG level induces high serum TG concentration. That is because VLDL is mainly composed of TG. But our previous research found that cholesterol feeding significantly increased the hepatic TG level, but reduced the serum TG content obviously as compared with the controls. So we came up with our hypothesis based on the above that incorporation of cholesterol ester (CE) into the VLDL particles takes priority amid VLDL assembly in comparison with TG in cholesterol-fed rats. In order to test and verify our hypothesis, we focused on the effect of dietary chole (...truncated)


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Yu-Ming Wang, Bei Zhang, Yong Xue, Zhao-Jie Li, Jing-Feng Wang, Chang-Hu Xue, Teruyoshi Yanagita. The mechanism of dietary cholesterol effects on lipids metabolism in rats, Lipids in Health and Disease, 2010, pp. 4, 9, DOI: 10.1186/1476-511X-9-4