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Journal of Lipid Research, Vol. 46, 2468-2476, November 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

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

Jogchum Plat^1,*, Jason A. Nichols and Ronald P. Mensink^*

^* Department of Human Biology, Maastricht University, 6200 MD Maastricht, The Netherlands
Assay Development and Compound Profiling, GlaxoSmithKline, Research Triangle Park, NC 27709

Published, JLR Papers in Press, September 8, 2005. DOI 10.1194/jlr.M500272-JLR200

¹ To whom correspondence should be addressed. e-mail: j.plat{at}hb.unimaas.nl

Plant stanols and sterols of the 4-desmethyl family (e.g., sitostanol and sitosterol) effectively decrease LDL cholesterol concentrations, whereas 4,4-dimethylsterols (-amyrin and lupeol) do not. Serum carotenoid concentrations, however, are decreased by both plant sterol families. The exact mechanisms underlying these effects are not known, although effects on micellar composition have been suggested. With a liver X receptor (LXR) coactivator peptide recruitment assay, we showed that plant sterols and stanols from the 4-desmethylsterol family activated both LXR and LXRß, whereas 4,4-dimethyl plant sterols did not. In fully differentiated Caco-2 cells, the functionality of this effect was shown by the 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 the effects of the 4-desmethyl family and 4,4-dimethylsterols on micellar carotenoid incorporation.

Our findings indicate that the decreased intestinal absorption of cholesterol and carotenoids by plant sterols and stanols is caused by two distinct mechanisms.

Abbreviations: ABC, ATP binding cassette; LXR, liver X receptor; SREBP-2, sterol-regulatory element binding protein-2

Supplementary key words cholesterol • antioxidant • ATP binding cassette transporter • liver X receptor

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