AJCN 19th International Congress of Nutrition
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American Journal of Clinical Nutrition, Vol. 84, No. 2, 312-321, August 2006
© 2006 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis in APOE*3Leiden mice1,2,3

Ilse Duivenvoorden, Peter J Voshol, Patrick CN Rensen, Wim van Duyvenvoorde, Johannes A Romijn, Jef J Emeis, Louis M Havekes and Willem F Nieuwenhuizen

1 From TNO Biomedical Research, Leiden, Netherlands (ID, PJV, PCNR, WvD, JJE, and LMH); TNO Innovative Ingredients and Products, Zeist, Netherlands (WFN); the Department of General Internal Medicine, University Medical Center, Leiden, Netherlands (ID, PCNR, and LMH); the Department of Endocrinology and Metabolic Diseases, University Medical Center, Leiden, Netherlands (PJV and JAR); and the Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands (LMH)

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.

Key Words: APOE*3Leiden mice • sphingolipids • steatosis • cholesterol • triacylglycerol • free fatty acids






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