Out Ruud, Kruijt J Kar, Rensen Patrick C N, Hildebrand Reeni B, de Vos Paula, Van Eck Miranda, Van Berkel Theo J C
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300 RA Leiden, The Netherlands.
J Biol Chem. 2004 Apr 30;279(18):18401-6. doi: 10.1074/jbc.M401170200. Epub 2004 Feb 17.
The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of high density lipoprotein (HDL) cholesterol esters is well established. However, the potential role of SR-BI in chylomicron and chylomicron remnant metabolism is largely unknown. In the present investigation, we report that the cell association of 160 nm-sized triglyceride-rich chylomicron-like emulsion particles to freshly isolated hepatocytes from SR-BI-deficient mice is greatly reduced (>70%), as compared with wild-type littermate mice. Competition experiments show that the association of emulsion particles with isolated hepatocytes is efficiently competed for (>70%) by the well established SR-BI ligands, HDL and oxidized low density lipoprotein (LDL), whereas LDL is ineffective. Upon injection into SR-BI-deficient mice the hepatic association of emulsion particles is markedly decreased ( approximately 80%) as compared with wild-type mice. The relevance of these findings for in vivo chylomicron (remnant) metabolism was further evaluated by studying the effect of SR-BI deficiency on the intragastric fat load-induced postprandial triglyceride response. The postprandial triglyceride response is 2-fold higher in SR-BI-deficient mice as compared with wild-type littermates (area-under-the-curve 39.6 +/- 1.2 versus 21.1 +/- 3.6; p < 0.005), with a 4-fold increased accumulation of chylomicron (remnant)-associated triglycerides in plasma at 6 h after intragastric fat load. We conclude that SR-BI is important in facilitating chylomicron (remnant) metabolism and might function as an initial recognition site for chylomicron remnants whereby the subsequent internalization can be exerted by additional receptor systems like the LDL receptor and LDL receptor-related protein.
I型B类清道夫受体（SR-BI）在介导高密度脂蛋白（HDL）胆固醇酯的选择性摄取中的作用已得到充分证实。然而，SR-BI在乳糜微粒和乳糜微粒残粒代谢中的潜在作用在很大程度上尚不清楚。在本研究中，我们报告，与野生型同窝小鼠相比，160纳米大小的富含甘油三酯的乳糜微粒样乳剂颗粒与SR-BI缺陷小鼠新鲜分离的肝细胞的细胞结合显著减少（>70%）。竞争实验表明，乳剂颗粒与分离的肝细胞的结合可被成熟的SR-BI配体HDL和氧化低密度脂蛋白（LDL）有效竞争（>70%），而LDL则无效。注射到SR-BI缺陷小鼠体内后，与野生型小鼠相比，乳剂颗粒的肝脏结合明显减少（约80%）。通过研究SR-BI缺陷对胃内脂肪负荷诱导的餐后甘油三酯反应的影响，进一步评估了这些发现对体内乳糜微粒（残粒）代谢的相关性。与野生型同窝小鼠相比，SR-BI缺陷小鼠的餐后甘油三酯反应高出2倍（曲线下面积39.6±1.2对21.1±3.6；p<0.005），胃内脂肪负荷后6小时血浆中乳糜微粒（残粒）相关甘油三酯的积累增加4倍。我们得出结论，SR-BI在促进乳糜微粒（残粒）代谢中很重要，可能作为乳糜微粒残粒的初始识别位点，随后的内化可由其他受体系统如LDL受体和LDL受体相关蛋白发挥作用。
