Abstract 439: Dietary Sphingomyelin Lowers Hepatic Lipids by Inhibiting Intestinal Cholesterol Absorption in High-Fat-Fed Mice

Abstract

Background: Accumulating evidence suggests that tissue sphingolipids such as sphingomyelin (SM) and ceramide contribute to the onset and development of atherosclerosis. Dietary sphingolipids may not however be pathogenic and we have shown that a phospholipid-rich extract from dairy milk that contains SM has potent liver lipid-lowering properties. Objective: To investigate the effect of pure dietary egg SM on hepatic lipid metabolism in high-fat fed mice. Methods: Four groups of male C57BL/6 mice were given a high-fat diet containing 21% w/w butterfat and 0.15% w/w cholesterol (HF) or the HF diet supplemented with egg SM (0.3, 0.6 or 1.2% w/w). After 4 weeks, livers were analysed for lipid and mRNA. Intestinal cholesterol absorption was measured with [14C]cholesterol and [3H]sitostanol in mice fed 0.6% w/w SM for three weeks. Results: All animals weighed similarly. Liver weight was significantly lower in 1.2%-fed mice (HF vs SM: 1.05 ± 0.03 v 0.86 ± 0.03 g, P < 0.05 by ANOVA). Total liver lipid (mg/organ) was significantly less in 0.6%SM- and 1.2%SM-fed mice (-33% and -40% vs HF resp., P < 0.001). This was due to significantly reduced levels of both triglyceride and cholesterol. Mice given 0.6%SM for 3 weeks were found to have significantly increased faecal lipid and cholesterol output and reduced liver accumulation of gastrically-administered [14C]cholesterol. Intestinal cholesterol absorption was significantly reduced by 0.6%SM supplementation (HF vs SM: 52.4 ± 2.6 vs 36.2 ± 3.5%, P < 0.01). Conclusion: Dietary egg sphingomyelin has pronounced lipid-lowering properties, suggesting it may have atheroprotective rather than atherogenic properties.