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Effects of apoA-II, C-I, C-II on in vivo metabolism of apoB-containing lipoproteins-stable, isotope study

apoA-II、C-I、C-II 对含 apoB 脂蛋白体内代谢的影响-稳定同位素研究

基本信息

批准号：
14571110
负责人：
IKEWAKI Katsunori
金额：
$ 1.73万
依托单位：
JIKEI UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571110/
关键词：
apolipoproteins lipoproteins stable isotope postprandiallipemia GC-MS

项目摘要

In addition to an elevated LDL-cholesterol (C), an increased triglyceride (TG) rich lipoprotein has drawn more attention as the risk for coronary artery disease. TG-rich lipoproteins (TRL) comprise heterogeneous lipoproteins subclasses, depending upon apoprotein composition. Among them, apoC-III and apoE have been extensively investigated, whereas effects of other apoptoteins such as apoA-II, C-I, C-II are largely unknown. In the present study, we wish to investigate 1) distribution of VLDL subcleasses which differ in apolipoprotein compositions, 2) in vivo role of apoC-III and apoE by utilyzing stable isotopically labeled amino acid tracer study. ApoA-II, C-I, and C-II containing VLDL comprise 13%, 17%, and 16% of VLDL, respectively, representing minor fractions among TRL relative to those containing either apoC-III or apoE. Those containing the apolipoproteins comprise more cholesterol and TG per particle and tend to have other apoproteins. Distribution does not change postprandially, but absolute concentrations increase by fat ingestion. In vivo kinetic study revealed that E-/C-and E-/C+ VLDL are catabolized faster than E+/C-and E+/C+ particles. This was true for IDL and LDL, too. ApoE containing particle, especially E+/C-, are preferentially catabolized by direct removal via LDL receptor or/and LRP with a delayed lipolysis. To the contrary, E-/C-and E-/C+ particles are catablized in favor of lipolysis rather than direct removal. In conclusions, these results demonstrated 1) that, unlike apoC-III and apoE, TRL containing apoA-II, apoC-I, or apoC-II represent minor fraction, thus not suitable for kinetic study. Combination of stable isotope tracer study with immunoaffinity isolation technique provides for the first time a new insight into the role of apoC-III and apoE on TRL, namely inhibitory effect of lipolysis and promoting direct uptake by apoE and promoting lipolysis by apoC-III.

除了低密度脂蛋白胆固醇(C)升高外，富含甘油三酯(TG)的脂蛋白作为冠状动脉疾病的风险引起了更多的关注。富含甘油三酯的脂蛋白(TRL)包括不同的脂蛋白亚类，这取决于载脂蛋白的组成。其中，apoC-III和apoE已被广泛研究，而其他凋亡素如apoA-II、C-I、C-II的作用尚不清楚。在本研究中，我们希望通过稳定的同位素标记氨基酸示踪剂研究1)载脂蛋白组成不同的VLDL亚链的分布，2)载脂蛋白C-III和载脂蛋白E在体内的作用。含有极低密度脂蛋白的载脂蛋白A-II、C-I和C-II分别占极低密度脂蛋白的13%、17%和16%，相对于含有载脂蛋白C-III或载脂蛋白E的载脂蛋白，TRL的比例很小。那些含有载脂蛋白的人每颗粒含有更多的胆固醇和甘油三酯，并倾向于含有其他载脂蛋白。餐后分布不会改变，但绝对浓度会因脂肪摄取而增加。体内动力学研究表明，E-/C-和E-/C+VLDL的降解速度快于E+/C-和E+/C+粒子。IDL和低密度脂蛋白也是如此。含有APOE的颗粒，尤其是E+/C-，优先通过低密度脂蛋白受体或/和LRP直接清除，然后延迟脂解。相反，E-/C-和E-/C+颗粒被催化，有利于脂肪分解，而不是直接去除。综上所述，这些结果表明：1)与apoC-III和apoE不同，含有apoA-II、apoC-I或apoC-II的TRL所占比例较小，因此不适合进行动力学研究。结合稳定同位素示踪研究和免疫亲和分离技术，首次对apoC-III和apoE在TRL中的作用提供了新的认识，即抑制脂解作用和促进apoE直接摄取和促进apoC-III的脂解作用。