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

除了LDL-胆固醇（C）升高外，富含甘油三酯（TG）的脂蛋白升高作为冠状动脉疾病的风险已引起更多关注。富TG脂蛋白（TRL）包括异质脂蛋白亚类，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apoA-II、C-I、C-II等apoteins的作用在很大程度上是未知的。本研究利用稳定同位素标记的氨基酸示踪技术，研究了载脂蛋白组成不同的VLDL亚基的分布，apoC-Ⅲ和apoE的体内作用。含有ApoA-II、C-I和C-II的VLDL分别占VLDL的13%、17%和16%，相对于含有apoC-III或apoE的TRL，它们在TRL中占较小比例。含有载脂蛋白的那些颗粒包含更多的胆固醇和TG，并且倾向于具有其他载脂蛋白。餐后分布没有变化，但绝对浓度增加脂肪摄入。体内动力学研究表明，E-/C-和E-/C+ VLDL比E+/C-和E+/C+颗粒降解更快。IDL和LDL也是如此。含有ApoE的颗粒，特别是E+/C-，优先通过LDL受体或/和LRP直接去除而分解代谢，延迟脂解。相反，E-/C-和E-/C+颗粒被分解有利于脂解而不是直接去除。总之，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占次要部分，因此不适合动力学研究。将稳定同位素示踪研究与免疫亲和分离技术相结合，首次为apoC-III和apoE对TRL的作用提供了新的认识，即抑制脂解作用和促进apoE直接摄取以及促进apoC-III脂解作用。

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.