Print Email Facebook Twitter Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis in APOE*3Leiden mice Title Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis in APOE*3Leiden mice Author Duivenvoorden, I. Voshol, P.J. Rensen, P.C.N. van Duyvenvoorde, W. Romijn, J.A. Emeis, J.J. Havekes, L.M. Nieuwenhuizen, W.F. TNO Kwaliteit van Leven Publication year 2006 Abstract Background: The prevalence of dyslipidemia and obesity resulting from excess energy intake and physical inactivity is increasing. The liver plays a pivotal role in systemic lipid homeostasis. Effective, natural dietary interventions that lower plasma lipids and promote liver health are needed. Objective: Our goal was to determine the effect of dietary sphingolipids on plasma lipids and liver steatosis. Design: APOE*3Leiden mice were fed a Western-type diet supplemented with different sphingolipids. Body cholesterol and triacylglycerol metabolism as well as hepatic lipid concentrations and lipid-related gene expression were determined. Results: Dietary sphingolipids dose-dependently lowered both plasma cholesterol and triacylglycerol in APOE*3Leiden mice; 1% phytosphingosine (PS) reduced plasma cholesterol and triacylglycerol by 57% and 58%, respectively. PS decreased the absorption of dietary cholesterol and free fatty acids by 50% and 40%, respectively, whereas intestinal triacylglycerol lipolysis was not affected. PS increased hepatic VLDL-triacylglycerol production by 20%, whereas plasma lipolysis was not affected. PS increased the hepatic uptake of VLDL remnants by 60%. Hepatic messenger RNA concentrations indicated enhanced hepatic lipid synthesis and VLDL and LDL uptake. The net result of these changes was a strong decrease in plasma cholesterol and triacylglycerol. The livers of 1% PS-fed mice were less pale, 22% lighter, and contained 61% less cholesteryl ester and 56% less triacylglycerol than livers of control mice. Furthermore, markers of liver inflammation (serum amyloid A) and liver damage (alanine aminotransferase) decreased by 74% and 79%, respectively, in PS-fed mice. Conclusion: Sphingolipids lower plasma cholesterol and triacylglycerol and protect the liver from fat- and cholesterol-induced steatosis. © 2006 American Society for Nutrition.Chemicals / CAS: alanine aminotransferase, 9000-86-6, 9014-30-6; amyloid, 11061-24-8; cholesterol, 57-88-5; phytosphingosine, 13552-11-9, 554-62-1; RNA, 63231-63-0; apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins E; Cholesterol, 57-88-5; Cholesterol, Dietary; Fatty Acids, Nonesterified; Lipoproteins, VLDL; RNA, 63231-63-0; Sphingolipids; Triglycerides Subject Health BiologyFood technologyAPOE*3Leiden miceCholesterolFree fatty acidsSphingolipidsSteatosisTriacylglycerolalanine aminotransferaseamyloidapolipoprotein E3cholesterolcholesterol esterfatty acidmessenger RNAphytosphingosineRNAsphingolipidtriacylglycerolapolipoprotein Eapolipoprotein E3 (Leidein)very low density lipoproteinanimal experimentanimal modelanimal tissuearticlecholesterol blood levelcholesterol metabolismcontrolled studydiet supplementationdose responsedrug effectdrug structurefatty liverfemalegene expressionhepatitislipogenesislipolysismousenonhumannutritional assessmentplasma clearanceprophylaxisanimalbloodchemistrycholesterol intakeenzymologyfecesgeneticsintestine absorptionlipid metabolismlivermetabolismphysiologyrandomizationtransgenic mouseAnimalsApolipoprotein E3Apolipoproteins ECholesterolCholesterol, DietaryDose-Response Relationship, DrugFatty Acids, NonesterifiedFatty LiverFecesFemaleGene ExpressionIntestinal AbsorptionLipid MetabolismLipolysisLipoproteins, VLDLLiverMiceMice, TransgenicRandom AllocationRNASphingolipidsTriglycerides To reference this document use: http://resolver.tudelft.nl/uuid:f3f647f8-2e36-47de-9ff3-75049bd9ed78 TNO identifier 239400 ISSN 0002-9165 Source American Journal of Clinical Nutrition, 84 (2), 312-321 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.