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

CaCo-2 cells were used to address the effect of the plant sterol, psitosterol, on cholesterol trafficking, choles- terol metabolism, and apoB secretion. Compared to cells in- cubated with micelles (5 mM taurocholate and 250 p~ 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 de- rived from the plasma membrane, 0-sitosterol did not alter cholesterol trafficking or cholesteryl ester secretion. Includ- ing psitosterol in the micelle together with cholesterol attenu- ated the influx of plasma membrane cholesterol and pre- vented the secretion of cholesteryl esters derived from the plasma membrane. Stigmasterol and campesterol had effects similar to psitosterol, although campesterol did promote a modest influx of plasma membrane cholesterol. Including p- sitosterol in the micelle with cholesterol decreased the uptake of cholesterol. Compared to cholesterol, 60% less p-sitosterol was taken up by CaCo-2 cells. No observable esterification of psitosterol was appreciated and the transport of the plant ste- rol to the basolateral medium was negligible. Cholesterol syn- thesis and HMGCoA reductase activities were decreased in cells incubated with p-sitosterol. This was associated with a de- crease in reductase mass and mRNA levels. Cholesteryl ester synthesis and ACAT activities were unaltered by p-sitosterol. Both stigmasterol and campesterol decreased reductase activ- ity, but only campesterol increased ACAT activity. psitosterol did not affect the secretion of apoB mass.Il The results sug- gest that p-sitosterol does not promote cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. p- sitosterol interferes with the uptake of micellar cholesterol causing less plasma membrane cholesterol to influx arid less cholesteryl ester to be secreted. Despite its lack of effect on cholesterol trafficking, psitosterol decreases cholesterol syn- thesis at the level of HMGCoA reductase genc expression.- Field, F. J., E. Born, and S. N. Mathur. Effect of micellar p- sitosterol on cholesterol metabolism in CaCo-2 crlls. ,I. I>i{id RES. 1997. 38: 348-360.