Journal of Lipid Research, Vol 38, 348-360, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

Effect of micellar beta-sitosterol on cholesterol metabolism in CaCo-2 cells

FJ Field, E Born and SN Mathur
Department of Internal Medicine, University of Iowa, Iowa City, USA.

CaCo-2 cells were used to address the effect of the plant sterol, beta- sitosterol, on cholesterol trafficking, cholesterol metabolism, and apoB secretion. Compared to cells incubated with micelles (5 mM taurocholate and 250 microM oleic acid) containing cholesterol, which caused an increase in the influx of plasma membrane cholesterol to the endoplasmic reticulum and increased the secretion of cholesteryl esters derived from the plasma membrane, beta-sitosterol did not alter cholesterol trafficking or cholesteryl ester secretion. Including beta- sitosterol in the micelle together with cholesterol attenuated the influx of plasma membrane cholesterol and prevented the secretion of cholesteryl esters derived from the plasma membrane. Stigmasterol and campesterol had effects similar to beta-sitosterol, although campesterol did not promote a modest influx of plasma membrane cholesterol. Including beta-sitosterol in the micelle with cholesterol decreased the uptake of cholesterol. Compared to cholesterol, 60% less beta-sitosterol was taken up by CaCo-2 cells. No observable esterification of beta-sitosterol was appreciated and the transport of the plant sterol to the basolateral medium was negligible. Cholesterol synthesis and HMG-CoA reductase activities were decreased in cells incubated with beta-sitosterol. This was associated with a decrease in reductase mass and mRNA levels. Cholesteryl ester synthesis and ACAT activities were unaltered by beta-sitosterol. Both stigmasterol and campesterol decreased reductase activity, but only campesterol increased ACAT activity. beta-sitosterol did not affect the secretion of apoB mass. The results suggest that beta-sitosterol does not promote cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. beta-sitosterol interferes with the uptake of micellar cholesterol causing less plasma membrane cholesterol to influx and less cholesteryl ester to be secreted. Despite its lack of effect on cholesterol trafficking, beta-sitosterol decreases cholesterol synthesis at the level of HMG-CoA reductase gene expression.
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