Abstract
The liver is responsible for controlling cholesterol homeostasis in the body. HMG-CoA reductase and the LDL receptor (LDL-r) are involved in this regulation and are also ubiquitously expressed in all major tissues. We have previously shown in guinea pigs that there is a correlation in gene expression of HMG-CoA reductase and the LDL-r between liver and mononuclear cells. The present study evaluated human mononuclear cells as a surrogate for hepatic expression of these genes. The purpose was to evaluate the effect of dietary carbohydrate restriction with low and high cholesterol content on HMG-CoA reductase and LDL-r mRNA expression in mononuclear cells. All subjects were counseled to consume a carbohydrate restricted diet with 10–15% energy from carbohydrate, 30–35% energy from protein and 55–60% energy from fat. Subjects were randomly assigned to either EGG (640 mg/d additional dietary cholesterol) or SUB groups [equivalent amount of egg substitute (0 dietary cholesterol contributions) per day] for 12 weeks. At the end of the intervention, there were no changes in plasma total or LDL cholesterol (LDL-C) compared to baseline (P > 0.10) or differences in plasma total or LDL-C between groups. The mRNA abundance for HMG-CoA reductase and LDL-r were measured in mononuclear cells using real time PCR. The EGG group showed a significant decrease in HMG-CoA reductase mRNA (1.98 ± 1.26 to 1.32 ± 0.92 arbitrary units P < 0.05) while an increase was observed for the SUB group (1.13 ± 0.52 to 1.69 ± 1.61 arbitrary units P < 0.05). Additionally, the LDL-r mRNA abundance was decreased in the EGG group (1.72 ± 0.69 to 1.24 ± 0.55 arbitrary units P < 0.05) and significantly increased in the SUB group (1.00 ± 0.60 to 1.67 ± 1.94 arbitrary units P < 0.05). The findings indicate that dietary cholesterol during a weight loss intervention alters the expression of genes regulating cholesterol homeostasis.
Highlights
Cholesterol is an important biological molecule that plays a role in membrane structure and it is a precursor for the synthesis of steroid hormones and bile acids [1,2]
In spite of the greater consumption of dietary cholesterol in the EGG group (877 mg/d) at wk 12 compared to the SUB group (277 mg/d), there were no increases in LDL cholesterol (LDL-C) between baseline and 12 wk or differences in LDLC between the EGG and the SUB groups
Mononuclear cells were used as a surrogate to reflect hepatic cholesterol homeostasis in response to a cholesterol challenge
Summary
Cholesterol is an important biological molecule that plays a role in membrane structure and it is a precursor for the synthesis of steroid hormones and bile acids [1,2]. It is a major player in the lipid rafts which have a vital role in cell signaling and protein sorting on the membrane sur-. Lipids in Health and Disease 2007, 6:34 http://www.lipidworld.com/content/6/1/34 face [3,4,5] Mammalian cells produce their own cholesterol and receive cholesterol by uptake from lipoproteins [5]. We demonstrated that increased intake of cholesterol affects mRNA expression of both HMG-CoA reductase and LDL-r
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