title: Dietary intake of plant sterols stably increases plant sterol levels in the murine brain.
abstract: Plant sterols such as sitosterol and campesterol are frequently administered as cholesterol-lowering supplements in food. Recently, it has been shown in mice that, in contrast to the structurally related cholesterol, circulating plant sterols can enter the brain. We questioned whether the accumulation of plant sterols in murine brain is reversible. After being fed a plant sterol ester-enriched diet for 6 weeks, C57BL/6NCrl mice displayed significantly increased concentrations of plant sterols in serum, liver, and brain by 2- to 3-fold. Blocking intestinal sterol uptake for the next 6 months while feeding the mice with a plant stanol ester-enriched diet resulted in strongly decreased plant sterol levels in serum and liver, without affecting brain plant sterol levels. Relative to plasma concentrations, brain levels of campesterol were higher than sitosterol, suggesting that campesterol traverses the blood-brain barrier more efficiently. In vitro experiments with brain endothelial cell cultures showed that campesterol crossed the blood-brain barrier more efficiently than sitosterol. We conclude that, over a 6-month period, plant sterol accumulation in murine brain is virtually irreversible.
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology,  University of Bonn, Bonn,  Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Vanmierlo
authors.forename: Oliver
authors.initials: O
authors.lastname: Weingärtner
authors.forename: Susanne
authors.initials: S
authors.lastname: van der Pol
authors.forename: Constanze
authors.initials: C
authors.lastname: Husche
authors.forename: Anja
authors.initials: A
authors.lastname: Kerksiek
authors.forename: Silvia
authors.initials: S
authors.lastname: Friedrichs
authors.forename: Eric
authors.initials: E
authors.lastname: Sijbrands
authors.forename: Harry
authors.initials: H
authors.lastname: Steinbusch
authors.forename: Marcus
authors.initials: M
authors.lastname: Grimm
authors.forename: Tobias
authors.initials: T
authors.lastname: Hartmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
authors.forename: Monique
authors.initials: M
authors.lastname: Mulder
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004032:Diet; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010840:Phytosterols / Q000008:administration & dosage* / Q000494:pharmacology; D012855:Sitosterols / Q000008:administration & dosage / Q000494:pharmacology; D013265:Stigmasterol / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
chemical_list: D010840:Phytosterols; D012855:Sitosterols; C021273:campesterol; C025473:gamma-sitosterol; D002784:Cholesterol; D013265:Stigmasterol