Plant sterols and stanols: Effects on mixed micellar composition and LXR (target gene) activation

Jogchum Plat, Jason A. Nichols, and Ronald P. Mensink

Human Biology, Maastricht University, Maastricht 6229 ER

Corresponding Author: J.PLAT{at}HB.UNIMAAS.NL

Plant stanols and sterols of the 4-desmethyl family (e.g. sitostanol and sitosterol) effectively lower LDL cholesterol concentrations, whereas 4,4 dimethyl sterols (alpha-amyrin and lupeol) do not. Serum carotenoid concentrations, however, are lowered by both plant sterol families. The exact mechanisms underlying these effects are not known, although effects on micellar composition have been suggested. With an LXR co-activator peptide recruitment assay, we showed that plant sterols and stanols from the 4-desmethylsterol family activated both LXRa and LXRb, while 4,4-dimethyl plant sterols did not. In fully differentiated caco-2 cells, functionality of this effect was shown by increased expression of ABCA1, one of the known LXR target genes expressed by caco-2 cells in measurable amounts. The LXR activating potential of the various plant sterols / stanols correlated positively with ABCA1 mRNA expression. Reductions in serum hydrocarbon carotenoids could be explained by effects of 4-desmethyl family and 4,4 dimethyl sterols on micellar carotenoid incorporation. Our findings therefore indicate that the lowered intestinal absorption of cholesterol and carotenoids by plant sterols and stanols are caused by two distinct mechanisms.

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