Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E. Accelerated clearance of lipoproteins containing apolipoprotein B.
Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E. Accelerated clearance of lipoproteins containing apolipoprotein B.
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DOI：
10.1172/jci116091
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发表时间：
1992-11
期刊：
影响因子：
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通讯作者：
Hitoshi Shimano;N. Yamada;Motoya Katsuki;Koji Yamamoto;T. Gotoda;K. Harada;M. Shimada;Y. Yazaki
中科院分区：
文献类型：
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作者：
Hitoshi Shimano;N. Yamada;Motoya Katsuki;Koji Yamamoto;T. Gotoda;K. Harada;M. Shimada;Y. Yazaki
我们报道过，过度表达大鼠apo E的转基因小鼠由于VLDL和LDL的消失而显示血浆胆固醇和甘油三酯水平显着降低。在这项研究中，我们研究了转基因小鼠血浆脂蛋白的代谢。静脉注射后，转基因小鼠的 125I-VLDL 和 125I-LDL 清除率分别比对照组高 3.0 倍和 2.4 倍。此外，通过口服视黄醇棕榈酸酯负载试验估计的乳糜微粒残留物的清除率在转基因小鼠中显着增强。免疫印迹分析显示两组 LDL 受体的肝脏表达相似。这些数据表明，含有apo B的脂蛋白的消除是由于这些富含apo E的脂蛋白通过肝LDL受体的清除增强所致。当喂食高胆固醇饮食时，对照组的血浆胆固醇水平升高两倍，凝胶过滤色谱上的 VLDL 和 LDL 胆固醇显着增加。相比之下，喂食胆固醇的转基因小鼠表现出对这些增加的抵抗力。高胆固醇喂养降低了转基因小鼠肝脏低密度脂蛋白受体的活性，并且对增强乳糜微粒残留清除没有影响。因此，apo E 的过度表达可能主要通过 LDL 受体途径并可能通过与乳糜微粒残余受体的相互作用促进含有 apo B 的脂蛋白的代谢。
We have reported that transgenic mice overexpressing rat apo E shows marked reduction of plasma cholesterol and triglyceride levels due to the disappearance of VLDL and LDL. In this study, we investigated the metabolism of plasma lipoproteins in transgenic mice. After intravenous injection, the rates of clearance of 125I-VLDL and 125I-LDL were 3.0- and 2.4-fold greater in transgenic mice than in controls, respectively. Furthermore, clearance of chylomicron remnants estimated by oral retinyl palmitate-loading test was markedly enhanced in transgenic mice. The hepatic expression of LDL receptors by immunoblot analysis was similar in both groups. These data suggest that elimination of lipoproteins containing apo B was due to enhanced clearance of these lipoproteins enriched with apo E through hepatic LDL receptors. When fed a high cholesterol diet, controls showed twofold elevation of plasma cholesterol levels with marked increases in VLDL and LDL cholesterol on gel filtration chromatography. In contrast, cholesterol-fed transgenic mice showed resistance against these increases. High cholesterol feeding decreased the activity of hepatic LDL receptors and had no effect on enhancement of chylomicron remnant clearance in transgenic mice. Thus, overexpression of apo E facilitates metabolism of lipoproteins containing apo B presumably primarily via the LDL receptor pathway and possibly through an interaction with the chylomicron remnant receptor.