Ishibashi S, Perrey S, Chen Z, Osuga J i, Shimada M, Ohashi K, Harada K, Yazaki Y, Yamada N
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
J Biol Chem. 1996 Sep 13;271(37):22422-7. doi: 10.1074/jbc.271.37.22422.
Two receptor pathways are thought to mediate the hepatic clearance of chylomicron remnants, (i) the low density lipoprotein receptor (LDLR) pathway and (ii) non-LDLR pathway. The current study was undertaken to quantitatively assess the contribution of each receptor pathway to hepatic catabolism of chylomicron remnants, by using mice that are deficient in apolipoprotein E (apoE) (apoE(-/-)), the LDLR (LDLR(-/-)), and both (apoE(-/-);LDLR(-/-)). Vitamin A fat tolerance tests showed that the area under the curves of the plasma excursions of retinyl ester in the LDLR(-/-), apoE(-/-), and apoE(-/-);LDLR(-/-) mice were 4, 12, and 12 times larger than those in wild-type mice. The retinyl ester accumulated in the plasma of the LDLR(-/-) mice was distributed in larger subfractions of triglyceride-rich lipoproteins, chylomicrons through very low density lipoprotein-C. These results indicate that the LDLR constitutes the major pathway for the clearance of retinyl ester. In support of this, agarose gel electrophoresis revealed that an oral fat load resulted in retention of chylomicrons in the LDLR(-/-) mice, which was not seen in wild-type mice. The observation that the apoE(-/-) mice showed larger retinyl ester excursion than LDLR(-/-) mice indicates that an apoE-dependent non-LDLR pathway is involved in the rest of the clearance of the retinyl ester. Together, we conclude that the LDLR pathway plays a significant role in the chylomicron remnant metabolism in mice fed a normal chow.
两条受体途径被认为介导乳糜微粒残粒的肝脏清除，（i）低密度脂蛋白受体（LDLR）途径和（ii）非LDLR途径。本研究旨在通过使用载脂蛋白E（apoE）缺陷型（apoE(-/-)）、LDLR缺陷型（LDLR(-/-)）以及两者均缺陷型（apoE(-/-);LDLR(-/-)）的小鼠，定量评估每条受体途径对乳糜微粒残粒肝脏分解代谢的贡献。维生素A耐脂试验表明，LDLR(-/-)、apoE(-/-)和apoE(-/-);LDLR(-/-)小鼠血浆视黄酯浓度曲线下面积分别是野生型小鼠的4倍、12倍和12倍。LDLR(-/-)小鼠血浆中积累的视黄酯分布在富含甘油三酯的脂蛋白的较大亚组分中，从乳糜微粒到极低密度脂蛋白-C。这些结果表明，LDLR构成视黄酯清除的主要途径。支持这一点的是，琼脂糖凝胶电泳显示口服脂肪负荷导致LDLR(-/-)小鼠中乳糜微粒潴留，而野生型小鼠中未见此现象。apoE(-/-)小鼠视黄酯浓度曲线下面积大于LDLR(-/-)小鼠这一观察结果表明，apoE依赖的非LDLR途径参与了视黄酯清除的其余部分。总之，我们得出结论，在喂食普通饲料的小鼠中，LDLR途径在乳糜微粒残粒代谢中起重要作用。
