title: Plant sterols and stanols: effects on mixed micellar composition and LXR (target gene) activation.
abstract: Plant stanols and sterols of the 4-desmethyl family (e.g., sitostanol and sitosterol) effectively decrease LDL cholesterol concentrations, whereas 4,4-dimethylsterols (alpha-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 LXRalpha and LXRbeta, 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.
authors.affiliation: Department of Human Biology, Maastricht University, 6200 MD Maastricht, The Netherlands. j.plat@hb.unimaas.nl
authors.forename: Jogchum
authors.initials: J
authors.lastname: Plat
authors.forename: Jason A
authors.initials: JA
authors.lastname: Nichols
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mensink
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D002338:Carotenoids / Q000737:chemistry; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D006838:Hydrocarbons / Q000737:chemistry; D007408:Intestinal Absorption; D007422:Intestines / Q000737:chemistry; D000071518:Liver X Receptors; D008823:Micelles; D008956:Models, Chemical; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D057093:Orphan Nuclear Receptors; D053978:Pentacyclic Triterpenes; D010455:Peptides / Q000737:chemistry; D010840:Phytosterols / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000737:chemistry; D012855:Sitosterols / Q000737:chemistry; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry; D000098825:Oxysterol Binding Proteins; D000094042:Lupanes
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000975:Antioxidants; D002338:Carotenoids; D002784:Cholesterol; D008078:Cholesterol, LDL; D004268:DNA-Binding Proteins; D006838:Hydrocarbons; D000071518:Liver X Receptors; D008823:Micelles; D009828:Oleanolic Acid; D057093:Orphan Nuclear Receptors; D053978:Pentacyclic Triterpenes; D010455:Peptides; D010840:Phytosterols; D010936:Plant Extracts; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012855:Sitosterols; D051782:Sterol Regulatory Element Binding Protein 2; D014315:Triterpenes; D000098825:Oxysterol Binding Proteins; C577836:ABCA1 protein, human; C000605213:NR1H3 protein, human; C497390:SREBF2 protein, human; C025473:gamma-sitosterol; C021255:stigmastanol; C036380:beta-amyrin; C010480:lupeol; D000094042:Lupanes