A Reappraisal of the Mechanism by Which Plant Sterols Promote Neutral Sterol Loss in Mice 英文参考文献.docVIP

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A Reappraisal of the Mechanism by Which Plant Sterols Promote Neutral Sterol Loss in Mice 英文参考文献.doc

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A Reappraisal of the Mechanism by Which Plant Sterols Promote Neutral Sterol Loss in Mice 英文参考文献

AReappraisaloftheMechanismbyWhichPlantSterols PromoteNeutralSterolLossinMice GemmaBrufau1*,FolkertKuipers2,YuguangLin3,ElkeA.Trautwein3,AlbertK.Groen2 1DepartmentofPediatrics,CenterforLiver,DigestiveandMetabolicDiseases,UniversityMedicalCenterGroningen,UniversityofGroningen,Groningen,TheNetherlands, 2DepartmentsofPediatricsandLaboratoryMedicine,CenterforLiver,DigestiveandMetabolicDiseases,UniversityMedicalCenterGroningen,UniversityofGroningen, Groningen,TheNetherlands,3UnileverRD,Vlaardingen,TheNetherlands Abstract Dietary plant sterols (PS) reduce serum total and LDL-cholesterol in hyperlipidemic animal models and in humans. This hypocholesterolemiceffectisgenerallyascribedtoinhibitionofcholesterolabsorption.However,whetherthiseffectfullyexplains thereportedstronginductionofneutralsterolexcretionuponplantsterolfeedingisnotknown.Recentdatademonstratethatthe intestinedirectlymediatesplasmacholesterolexcretionintofeces,i.e.,withoutinvolvementofthehepato-biliaryroute. Objective: Aimof thisstudywas to determinewhetherstimulation offecalneutralsterol lossduringPSfeedingis(partly) explainedbyincreasedintestinalcholesterolexcretionandtoassesstheroleofthecholesteroltransporterAbcg5/Abcg8herein. MethodsandResults:Wild-typemicewerefedacontroldietordietsenrichedwithincreasingamountsofPS(1%,2%,4% or8%,wt/wt)fortwoweeks.Inaddition,Abcg5-/-micewerefedeithercontrolor8%PSdiet.PSfeedingresultedinadose- dependentdecreaseoffractionalcholesterolabsorption(,2–7-foldreduction)inwild-typemiceand,80%reductionin -/- Abcg5 mice.Furthermore,PSfeedingledtoastrong,dose-independentinductionofneutralsterolexcretion(3.4-foldin wild-typesand2.7-foldinAbcg5-/-mice)withoutchangesinbiliarycholesterolsecretion.ItwascalculatedthatPSfeeding stimulatedintestinalcholesterolexcretionby,500%inwild-typemiceandby,250%inAbcg5-/-. Conclusions: Our data indicate that in mice the cholesterol-lowering effects of PS are to a large extent attributable to stimulation of intestinal, non-bile derived, cholesterol e