Apolipoprotein B48 metabolism in chylomicrons and very low-density lipoproteins and its role in triglyceride transport in normo- and hypertriglyceridemic human subjects
Apolipoprotein B48 metabolism in chylomicrons and very low-density lipoproteins and its role in triglyceride transport in normo- and hypertriglyceridemic human subjects
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DOI：
10.1111/joim.13017
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发表时间：
2020-01-07
影响因子：
11.1
通讯作者：
Boren, J.
中科院分区：
文献类型：
--
作者：
Bjornson, E.;Packard, C. J.;Boren, J.
背景：对富含甘油三酯的脂蛋白作为心血管疾病的病原体的重新关注，要求进一步探索乳糜微粒和极低密度脂蛋白（VLDL）的综合代谢。方法采用新型示踪技术和综合多室室模型，测定了15名血浆甘油三酯水平范围较宽的受试者乳糜微粒和VLDL密度区间内含载脂蛋白48-和载脂蛋白100颗粒的动力学。结果在高脂饮食后，载脂蛋白48出现在所有受试者的乳糜微粒、VLDL1和VLDL2部分。乳糜微粒从循环中迅速清除，但含有载脂蛋白48的VLDL积累，血浆甘油三酯高与低的患者在一天内的含量高3倍。含载脂蛋白48的颗粒直接分泌到乳糜微粒和VLDL组分中，其速率在所研究的血浆甘油三酯范围内相似。在脂肪吸收过程中，虽然大多数甘油三酯进入乳糜微粒循环，但大多数载脂蛋白48颗粒被分泌到VLDL密度范围内。结论在基础状态和饲粮脂质吸收过程中，肠道不仅以乳糜微粒的形式分泌含载脂蛋白48颗粒，而且直接进入VLDL1和VLDL2密度范围。在一天中，含载脂蛋白48的颗粒似乎占循环VLDL的20-25%，特别是在甘油三酯升高的人群中，形成缓慢清除的“残余”颗粒群的一部分，因此可能增加冠心病的风险。这些发现提供了一种代谢理解，当脂肪分解缓慢导致残留物积聚时，特别是在高甘油三酯血症患者中，可能会增加冠心病风险。
Background Renewed interest in triglyceride-rich lipoproteins as causative agents in cardiovascular disease mandates further exploration of the integrated metabolism of chylomicrons and very low-density lipoproteins (VLDL). Methods Novel tracer techniques and an integrated multi-compartmental model were used to determine the kinetics of apoB48- and apoB100-containing particles in the chylomicron and VLDL density intervals in 15 subjects with a wide range of plasma triglyceride levels. Results Following a fat-rich meal, apoB48 appeared in the chylomicron, VLDL1 and VLDL2 fractions in all subjects. Chylomicrons cleared rapidly from the circulation but apoB48-containing VLDL accumulated, and over the day were 3-fold higher in those with high versus low plasma triglyceride. ApoB48-containing particles were secreted directly into both the chylomicron and VLDL fractions at rates that were similar across the plasma triglyceride range studied. During fat absorption, whilst most triglyceride entered the circulation in chylomicrons, the majority of apoB48 particles were secreted into the VLDL density range. Conclusion The intestine secretes apoB48-containing particles not only as chylomicrons but also directly into the VLDL1 and VLDL2 density ranges both in the basal state and during dietary lipid absorption. Over the day, apoB48-containing particles appear to comprise about 20-25% of circulating VLDL and, especially in those with elevated triglycerides, form part of a slowly cleared 'remnant' particle population, thereby potentially increasing CHD risk. These findings provide a metabolic understanding of the potential consequences for increased CHD risk when slowed lipolysis leads to the accumulation of remnants, especially in individuals with hypertriglyceridemia.