van Bennekum Ariëtte, Werder Moritz, Thuahnai Stephen T, Han Chang-Hoon, Duong Phu, Williams David L, Wettstein Philipp, Schulthess Georg, Phillips Michael C, Hauser Helmut
Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4318, USA.
Biochemistry. 2005 Mar 22;44(11):4517-25. doi: 10.1021/bi0484320.
There is now a general consensus that the intestinal absorption of water-insoluble, dietary lipids is protein-mediated, but the assignment of protein(s) to this function is still a matter of debate. To address this issue, we measured beta-carotene and cholesterol absorption in wild-type and SR-BI knockout mice and the uptake of these lipids in vitro using brush border membrane (BBM) vesicles. From the comparison of the in vivo and in vitro results we conclude that both BBM-resident class B scavenger receptors, SR-BI and CD36, can facilitate the absorption of beta-carotene and cholesterol. SR-BI is essential for beta-carotene absorption, at least in mice on a high fat diet. This is due to the fact that the absorption of beta-carotene is restricted to the duodenum and SR-BI is the predominant receptor in the mouse duodenum. In contrast, SR-BI may be involved but is not essential for cholesterol absorption in the small intestine. The question of whether SR-BI contributes to cholesterol absorption in vivo is still unresolved. Transfection of COS-7 cells with SR-BI or CD36 confers on these cells lipid uptake properties closely resembling those of enterocytes and BBM vesicles. Both scavenger receptors facilitate the uptake of dietary lipids such as beta-carotene, free and esterified cholesterol, phospholipids, and fatty acids into COS-7 cells. This lipid uptake is effected from three different lipid donor particles: mixed bile salt micelles, phospholipid small unilamellar vesicles, and trioleoylglycerol emulsions which are all likely to be present in the small intestine. Ezetimibe, a representative of a new class of drugs that inhibit intestinal cholesterol absorption, blocks SR-BI- and CD36-facilitated uptake of cholesterol into COS-7 cells.
目前已形成普遍共识，即水不溶性膳食脂质的肠道吸收是由蛋白质介导的，但具体是哪种蛋白质发挥此功能仍存在争议。为解决这一问题，我们测定了野生型和SR-BI基因敲除小鼠体内β-胡萝卜素和胆固醇的吸收情况，并利用刷状缘膜（BBM）囊泡在体外检测了这些脂质的摄取。通过比较体内和体外实验结果，我们得出结论：BBM中驻留的B类清道夫受体SR-BI和CD36均可促进β-胡萝卜素和胆固醇的吸收。SR-BI对β-胡萝卜素的吸收至关重要，至少在高脂饮食的小鼠中如此。这是因为β-胡萝卜素的吸收局限于十二指肠，而SR-BI是小鼠十二指肠中的主要受体。相比之下，SR-BI可能参与小肠胆固醇的吸收，但并非必不可少。SR-BI在体内是否有助于胆固醇吸收的问题仍未解决。用SR-BI或CD36转染COS-7细胞后，这些细胞的脂质摄取特性与肠上皮细胞和BBM囊泡非常相似。两种清道夫受体都能促进膳食脂质如β-胡萝卜素、游离和酯化胆固醇、磷脂及脂肪酸进入COS-7细胞。这种脂质摄取是通过三种不同的脂质供体颗粒实现的：混合胆盐微团、磷脂小单层囊泡和三油酰甘油乳剂，而这些在小肠中都可能存在。新型肠道胆固醇吸收抑制剂依泽替米贝可阻断SR-BI和CD36介导的胆固醇进入COS-7细胞的摄取过程。
