Department of Nutrition, Chinese People Liberation Army (PLA) General Hospital, Beijing, 100853, China.
Food Funct. 2017 Jan 25;8(1):291-298. doi: 10.1039/c6fo01207h.
Hypercholesterolemia is one of the important risk factors of atherosclerosis (AS). The aim of this study is to explore the effect of medium-chain fatty acids (MCFAs) on serum cholesterol levels and their mechanism of action. Hyperlipemia, as a model of abnormal lipid hypermetabolism, was established by using a high fat diet in C57BL/6J mice. Forty eight mice with dyslipidemia were randomly divided into 4 groups, 12 mice per group, including the control group, the 2% caprylic acid (C8:0)-treated group, 2% capric acid (C10:0)-treated group, and 2% oleic acid (C18:1)-treated group. All mice were fed with a high fat diet. After 16 weeks, the mice were anesthetized with chloral hydrate. The mouse portal vein blood, the liver and the start site of the ileum (1 cm) were collected. The body weight of the mice and blood lipid profiles were measured. Gene transcription and the expression level associated with bile acid metabolism in the liver and small intestine were determined by real-time PCR and the western blotting method. The concentrations of bile acid metabolites in bile and feces were analysed. After 16 weeks of treatment, the concentrations of TC and LDL-C in the caprylic acid group were significantly lower than those in the control group (P < 0.05); the transcription and expression level of LXR, CYP7A1, CYP27A1 and ABCG8 in the caprylic acid and capric acid groups were significantly higher than those in the control group in the liver (P < 0.05), however the transcription and expression level of the small heterodimer partner (SHP) were significantly lower than those in the control group (P < 0.05); the transcription and expression level of LXR, ABCG5 and ABCG8 in the caprylic acid, capric acid and oleic acid groups were significantly higher than those in the control group in the small intestine (P < 0.05). The concentrations of total bile acid, mainly cholic acid and cholesterol in bile and feces were significantly higher in the caprylic and capric acid groups than those of in the control group (P < 0.05). Thus, MCFA increased the expression of LXR and ABCG8, enhanced CYP7A1 and CYP27A1 expression, decreased and SHP expression in the liver, thereby promoted liver bile acid synthesis and excretion. In addition MCFA increased the expression of ABCG5, ABCG8 and LXR in the small intestine, thereby inhibiting small intestinal bile acid absorption, increasing the concentrations of cholesterol and bile acid in bile and feces and reducing the level of serum cholesterol.
高胆固醇血症是动脉粥样硬化（AS）的重要危险因素之一。本研究旨在探讨中链脂肪酸（MCFAs）对血清胆固醇水平的影响及其作用机制。通过高脂饮食建立 C57BL/6J 小鼠高脂血症模型。将 48 只高脂血症小鼠随机分为 4 组，每组 12 只，分别为对照组、2%辛酸（C8:0）处理组、2%癸酸（C10:0）处理组和 2%油酸（C18:1）处理组。所有小鼠均给予高脂饮食。16 周后，用氯仿麻醉小鼠。采集小鼠门静脉血、肝脏和回肠起始部位（1cm）。测量小鼠体重和血脂谱。通过实时 PCR 和 Western blot 法测定肝脏和小肠与胆汁酸代谢相关的基因转录和表达水平。分析胆汁和粪便中胆汁酸代谢物的浓度。治疗 16 周后，辛酸组 TC 和 LDL-C 浓度明显低于对照组（P<0.05）；在肝脏中，辛酸和癸酸组 LXR、CYP7A1、CYP27A1 和 ABCG8 的转录和表达水平明显高于对照组（P<0.05），但小异二聚体伴侣（SHP）的转录和表达水平明显低于对照组（P<0.05）；在小肠中，辛酸、癸酸和油酸组 LXR、ABCG5 和 ABCG8 的转录和表达水平明显高于对照组（P<0.05）。胆汁和粪便中总胆汁酸、主要胆酸和胆固醇的浓度在辛酸和癸酸组明显高于对照组（P<0.05）。因此，MCFA 增加了 LXR 和 ABCG8 的表达，增强了 CYP7A1 和 CYP27A1 的表达，降低了 SHP 的表达，从而促进了肝脏胆汁酸的合成和排泄。此外，MCFA 增加了小肠中 ABCG5、ABCG8 和 LXR 的表达，从而抑制了小肠胆汁酸的吸收，增加了胆汁和粪便中胆固醇和胆汁酸的浓度，降低了血清胆固醇水平。
