Hypercholesterolemia and apolipoprotein B expression: regulation by selenium status.

Sanjiv Dhingra,Mohinder P Bansal

doi:10.1186/1476-511x-4-28

Abstract

BackgroundApolipoprotein B (apoB) contains ligand-binding domain for the binding of LDL to LDL-R site, which enables the removal of LDL from circulation. Our recent data showed that selenium (Se) is involved in the lipid metabolism. The present study was aimed to understand the effect of Se deficiency (0.02 ppm) and selenium supplementation (1 ppm) on apoB expression in liver during hypercholesterolemia in male Sprague Dawley rats. Animals were fed with control and high cholesterol diet (2%) for 1 and 2 months. ApoB levels by ELISA and protein expression by western blot was done. Hepatic LDL receptor (LDL-R) activity (in vivo) and mRNA expression by RT-PCR was monitored.ResultsIn selenium deficiency and on high cholesterol diet (HCD) feeding apoB levels increased and LDL-R expression decreased significantly after 2 months. On 1 ppm selenium supplementation apoB expression significantly decreased and LDL-R expression increased after 2 months. But after one month of treatment there was no significant change observed in apoB and LDL-R expression.ConclusionSo the present study demonstrates that Se deficiency leads to up regulation of apoB expression during experimental hypercholesterolemia. Selenium supplementation upto 1 ppm leads to downregulation of apoB expression. Further, this study will highlight the nutritional value of Se supplementation in lipid metabolism.

Highlights

Apolipoprotein B contains ligand-binding domain for the binding of LDL to LDL receptor (LDL-R) site, which enables the removal of LDL from circulation
Se adequate and excess diet was prepared from Se deficient diet by supplementing it with 0.2 ppm and 1 ppm of Se as sodium selenite (Sigma Chemicals). 2% of cholesterol (LobaChemie, India) was added to the respective high cholesterol diet (HCD) groups. These results form the basis for a model that selenium status in the body regulates apolipoprotein B expression through selenoenzyme, 5'iodothyronine deiodinase (5'-DI)
Selenium deficiency leads to decreased expression of 5'-DI, decreased T3 levels and decrease in LDL-cholesterol removal from blood through downregulation of LDL-R mRNA expression, decreased Apolipoprotein B (apoB) catabolism through LDL receptors

Summary

Introduction

Apolipoprotein B (apoB) contains ligand-binding domain for the binding of LDL to LDL-R site, which enables the removal of LDL from circulation. The interaction between LDL and LDL receptor has a major role in determining plasma cholesterol levels [1,2] and apolipoprotein B (apoB) has the central role in this ligand-receptor interaction. Plasma apoB levels maybe a better assay of the concentration of atherogenic lipoproteinparticles than total or LDL cholesterol levels [7]. A cross-sectional study in patients who had coronary arterybypass graft surgery determined that apoB concentration wasa better discriminator than LDL cholesterol concentration inpredicting recurrent atherosclerotic disease in bypass grafts years after surgery [8]. Abnormalities in the apoB metabolism are responsible for the generation of hypercholesterolemia and increased risk of coronary heart disease [9]. Abraham et al [11] have found a significantly increased production of apoB levels in cul-

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