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.
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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)