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膳食鞘脂可降低APOE*3 Leiden小鼠的血浆胆固醇和甘油三酯,并预防肝脏脂肪变性。

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

作者信息

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

机构信息

TNO Biomedical Research, Leiden, Netherlands.

出版信息

Am J Clin Nutr. 2006 Aug;84(2):312-21. doi: 10.1093/ajcn/84.1.312.

DOI:10.1093/ajcn/84.1.312
PMID:16895877
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.

摘要

背景

因能量摄入过多和缺乏身体活动导致的血脂异常和肥胖症患病率正在上升。肝脏在全身脂质稳态中起关键作用。需要有效的天然饮食干预措施来降低血脂并促进肝脏健康。

目的

我们的目标是确定膳食鞘脂对血脂和肝脏脂肪变性的影响。

设计

给载脂蛋白E*3 Leiden小鼠喂食补充了不同鞘脂的西式饮食。测定了身体胆固醇和三酰甘油代谢以及肝脏脂质浓度和脂质相关基因表达。

结果

膳食鞘脂可使载脂蛋白E*3 Leiden小鼠的血浆胆固醇和三酰甘油呈剂量依赖性降低;1%的植物鞘氨醇(PS)分别使血浆胆固醇和三酰甘油降低了57%和58%。PS分别使膳食胆固醇和游离脂肪酸的吸收降低了50%和40%,而肠道三酰甘油脂解未受影响。PS使肝脏极低密度脂蛋白三酰甘油的生成增加了20%,而血浆脂解未受影响。PS使肝脏对极低密度脂蛋白残粒的摄取增加了60%。肝脏信使核糖核酸浓度表明肝脏脂质合成以及极低密度脂蛋白和低密度脂蛋白摄取增强。这些变化的最终结果是血浆胆固醇和三酰甘油大幅降低。与对照小鼠的肝脏相比,喂食1% PS的小鼠的肝脏颜色不那么苍白体重轻22%,胆固醇酯含量减少61%,三酰甘油含量减少56%。此外,喂食PS的小鼠肝脏炎症标志物(血清淀粉样蛋白A)和肝损伤标志物(丙氨酸转氨酶)分别降低了74%和79%。

结论

鞘脂可降低血浆胆固醇和三酰甘油,并保护肝脏免受脂肪和胆固醇诱导的脂肪变性。

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