Oxidation of sitosterol and transport of its 7-oxygenated products from different tissues in humans and ApoE knockout mice

dc.contributor.authorSchött, Hans-Frieder
dc.contributor.authorBaumgartner, Sabine
dc.contributor.authorHusche, Constanze
dc.contributor.authorLuister, Alexandra
dc.contributor.authorFriedrichs, Silvia
dc.contributor.authorMiller, Charlotte M.
dc.contributor.authorMcCarthy, Florence O.
dc.contributor.authorPlat, Jogchum
dc.contributor.authorLaufs, Ulrich
dc.contributor.authorWeingärtner, Oliver
dc.contributor.authorLütjohann, Dieter
dc.contributor.funderUniversität des Saarlandesen
dc.contributor.funderNederlandse Organisatie voor Wetenschappelijk Onderzoeken
dc.contributor.funderSeventh Framework Programmeen
dc.date.accessioned2018-02-12T10:17:04Z
dc.date.available2018-02-12T10:17:04Z
dc.date.issued2016-04-27
dc.date.updated2018-02-06T11:12:45Z
dc.description.abstractThe most common phytosterols in the human diet are sitosterol and campesterol, which originate exclusively from plant derived food. These phytosterols are taken up by NPC1L1 transport from the intestine into the enterocytes together with cholesterol and other xenosterols. Phytosterols are selectively pumped back from the enterocytes into the intestinal lumen and on the liver site from hepatocytes into bile by heterodimeric ABCG5/G8 transporters. Like cholesterol, both phytosterols are prone to ring and side chain oxidation. It could be shown that oxyphytosterols, found in atherosclerotic tissue, are most likely of in situ oxidation (Schött et al.; Biochem. Biophys. Res. Commun. 2014 Apr 11;446(3):805-10). However, up to now, the entire mechanism of phytosterol oxidation is not clearly understood. Here, we provide further information about the oxidation of sitosterol and the transport of its oxidation products out of tissue. Our survey includes data of 104 severe aortic stenosis patients that underwent an elective aortic valve cusp replacement. We studied their phytosterol concentrations, as well as absolute and substrate corrected oxyphytosterol levels in plasma and valve cusp tissue. In addition, we also examined phytosterol and oxyphytosterol concentrations in plasma and tissues (from brain and liver) of 10 male ApoE knockout mice. The ratio of 7-oxygenated-sitosterol-to-sitosterol exceeds the ratio for 7-oxygenated-campesterol-to-campesterol in plasma and tissue of both humans and mice. This finding indicates that sitosterol is oxidized to a higher amount than campesterol and that a selective oxidative mechanism might exist which can differentiate between certain phytosterols. Secondly, the concentrations of oxyphytosterols found in plasma and tissue support the idea that oxysitosterols are preferably transported out of individual tissues. Selective oxidation of sitosterol and preferred transport of sitosterol oxidation products out of tissue seem to be a metabolic pathway of forced sitosterol clearance from tissue compartments.en
dc.description.sponsorshipNederlandse Organisatie voor Wetenschappelijk Onderzoek (Grant 014-012-010; NWO TOP Grant No. 91208006)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSchött, H.-F., Baumgartner, S., Husche, C., Luister, A., Friedrichs, S., Miller, C. M., McCarthy, F. O., Plat, J., LaufS, U., Weingärtner, O. and Lütjohann, D. (2017) ‘Oxidation of sitosterol and transport of its 7-oxygenated products from different tissues in humans and ApoE knockout mice’, Journal of Steroid Biochemistry and Molecular Biology, 169, pp. 145-151. doi:10.1016/j.jsbmb.2016.04.011en
dc.identifier.doi10.1016/j.jsbmb.2016.04.011
dc.identifier.endpage151en
dc.identifier.issn0960-0760
dc.identifier.journaltitleJournal of Steroid Biochemistry and Molecular Biologyen
dc.identifier.startpage145en
dc.identifier.urihttps://hdl.handle.net/10468/5438
dc.identifier.volume169en
dc.language.isoenen
dc.publisherElsevier Ltd.en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/211696/EU/THERAPEUTIC AND PREVENTIVE IMPACT OF NUTRITIONAL LIPIDS ON NEURONAL AND COGNITIVE PERFORMANCE IN AGING, ALZHEIMER’S DISEASE AND VASCULAR DEMENTIA/LIPIDIDIETen
dc.rights© 2016, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectSitosterolen
dc.subjectPhytosterolen
dc.subjectOxyphytosterolen
dc.subjectOxidationen
dc.subjectTransporten
dc.subjectMetabolismen
dc.titleOxidation of sitosterol and transport of its 7-oxygenated products from different tissues in humans and ApoE knockout miceen
dc.typeArticle (peer-reviewed)en
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