Mechanism of Resistance to Dietary Cholesterol

Abstract

Background. Alterations in expression of hepatic genes that could contribute to resistance to dietary cholesterol were investigated in Sprague-Dawley rats, which are known to be resistant to the serum cholesterol raising action of dietary cholesterol. Methods. Microarray analysis was used to provide a comprehensive analysis of changes in hepatic gene expression in rats in response to dietary cholesterol. Changes were confirmed by RT-PCR analysis. Western blotting was employed to measure changes in hepatic cholesterol 7α hydroxylase protein. Results. Of the 28,000 genes examined using the Affymetrix rat microarray, relatively few were significantly altered. As expected, decreases were observed for several genes that encode enzymes of the cholesterol biosynthetic pathway. The largest decreases were seen for squalene epoxidase and lanosterol 14α demethylase (CYP 51A1). These changes were confirmed by quantitative RT-PCR. LDL receptor expression was not altered by dietary cholesterol. Critically, the expression of cholesterol 7α hydroxylase, which catalyzes the rate-limiting step in bile acid synthesis, was increased over 4-fold in livers of rats fed diets containing 1% cholesterol. In contrast, mice, which are not resistant to dietary cholesterol, exhibited lower hepatic cholesterol 7α hydroxylase (CYP7A1) protein levels, which were not increased in response to diets containing 2% cholesterol.

Coenzyme Q10 supplementation improves metabolic parameters, liver function and mitochondrial respiration in rats with high doses of atorvastatin and a cholesterol-rich diet

“…Results from other studies show a lower activity of HMG-CoA reductase and lower expression of LDL receptors in the liver from rats fed a high fat diet [27]. Our study showed a significant decrease of cholesterol and triacylglycerol levels in the liver of animals treated with ATV and CoQ 10 , compared with those rats that only received ATV.…”

Mathematically modelling the dynamics of cholesterol metabolism and ageing

“…Conversely, Spady and Cuthbert (1992) observed that rats on fed high levels of dietary cholesterol, did not exhibit suppressed hepatic LDLr activity despite a 350-fold increase in hepatic cholesterol ester levels (Spady and Cuthbert, 1992). More recently, Boone et al (2011) found that LDLr expression in Sprague-Dawley rats was not altered by dietary cholesterol. There was also a significant increase in mean hepatic cholesterol and paradoxically a decrease in serum cholesterol (Boone et al, 2011).…”

“…More recently, Boone et al (2011) found that LDLr expression in Sprague-Dawley rats was not altered by dietary cholesterol. There was also a significant increase in mean hepatic cholesterol and paradoxically a decrease in serum cholesterol (Boone et al, 2011). However, other studies in humans, such as Lichtenstein et al (1993) demonstrate that the addition of dietary cholesterol (~1.5 eggs per/day) to a corn oil-diet, can result in a significant increase in concentrations of total cholesterol (6%), LDL-C (8%), and HDL-C (7%), when compared to diets with low dietary cholesterol, in 14 middle-aged and older individuals.…”

The effect of taurine on cholesterol metabolism

“…Boone et al. [] also reported that western blotting analysis showed dietary cholesterol significantly increases CYP7A1 protein levels in rats but not in mice. Other reports [] showed that dietary cholesterol may act to increase or decrease CYP7A1 mRNA levels in C57BL/6J mice depending on the type of fat added to the diet, and olive oil supplement caused increased expression of CYP7A1.…”