Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis in APOE*3Leiden mice
article
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
Topics
Food technologyAPOE*3Leiden miceCholesterolFree fatty acidsSphingolipidsSteatosisTriacylglycerolAlanine aminotransferaseAmyloidApolipoprotein E3CholesterolCholesterol esterFatty acidMessenger RNAPhytosphingosineRNASphingolipidTriacylglycerolApolipoprotein EApolipoprotein E3 (Leidein)Very low density lipoproteinAnimal experimentAnimal modelAnimal tissueCholesterol 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
TNO Identifier
239400
ISSN
00029165
Source
American Journal of Clinical Nutrition, 84(2), pp. 312-321.
Pages
312-321
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