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Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis in APOE*3Leiden mice

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Author: Duivenvoorden, I. · Voshol, P.J. · Rensen, P.C.N. · Duyvenvoorde, W. van · Romijn, J.A. · Emeis, J.J. · Havekes, L.M. · Nieuwenhuizen, W.F.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:American Journal of Clinical Nutrition, 2, 84, 312-321
Identifier: 239400
Keywords: Health Biology · Food technology · APOE*3Leiden mice · Cholesterol · Free fatty acids · Sphingolipids · Steatosis · Triacylglycerol · alanine aminotransferase · amyloid · apolipoprotein E3 · cholesterol · cholesterol ester · fatty acid · messenger RNA · phytosphingosine · RNA · sphingolipid · triacylglycerol · apolipoprotein E · apolipoprotein E3 (Leidein) · very low density lipoprotein · animal experiment · animal model · animal tissue · article · cholesterol blood level · cholesterol metabolism · controlled study · diet supplementation · dose response · drug effect · drug structure · fatty liver · female · gene expression · hepatitis · lipogenesis · lipolysis · mouse · nonhuman · nutritional assessment · plasma clearance · prophylaxis · animal · blood · chemistry · cholesterol intake · enzymology · feces · genetics · intestine absorption · lipid metabolism · liver · metabolism · physiology · randomization · transgenic mouse · Animals · Apolipoprotein E3 · Apolipoproteins E · Cholesterol · Cholesterol, Dietary · Dose-Response Relationship, Drug · Fatty Acids, Nonesterified · Fatty Liver · Feces · Female · Gene Expression · Intestinal Absorption · Lipid Metabolism · Lipolysis · Lipoproteins, VLDL · Liver · Mice · Mice, Transgenic · Random Allocation · RNA · Sphingolipids · Triglycerides

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