NPC1L1 and SR-BI are involved in intestinal cholesterol absorption from small-size lipid donors

被引:26
作者
Haikal, Ziad [1 ,2 ]
Play, Barbara [1 ,2 ]
Landrier, Jean-Francois [1 ,2 ]
Giraud, Annie [1 ,2 ]
Ghiringhelli, Odette [1 ,2 ]
Lairon, Denis [1 ,2 ]
Jourdheuil-Rahmani, Dominique [1 ,2 ]
机构
[1] Univ Aix Marseille 2, Univ Aix Marseille 1, U476,INRA,INSERM, UMR Nutriments Lipid & Prevent Malad Metab 1260, F-13385 Marseille, France
[2] Univ Aix Marseille 2, Fac Med, IPHM, IFR, F-13385 Marseille, France
关键词
cholesterol absorption; NPC1L1; SR-BI; bile acids; vesicle; mixed micelles;
D O I
10.1007/s11745-008-3172-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In the human intestinal content after a meal, cholesterol is dispersed in a complex mixture of emulsified droplets, vesicles, mixed micelles and precipitated material. The aim of this study was to determine the contribution of the main intestinal cholesterol transporters (NPC1L1, SR-BI) to the absorption processes, using different cholesterol-solubilizing donors. Cholesterol donors prepared with different taurocholate concentrations were added to an apical medium of differentiated TC7/Caco-2 cells. As the taurocholate concentrations increased, cholesterol donor size decreased (from 712 to 7 nm in diameter), which enhanced cholesterol absorption in a dose-dependent manner (38-fold). Two transport processes were observed: (1) absorption from large donors exhibited low-capacity transport with no noticeable transporter contribution; (2) efficient cholesterol absorption occurs from small lipid donors (<= 23 nm diameter), mainly due to NPC1L1 and SR- BI involvement. In addition, bile acids significantly increased mRNA and protein expression of NPC1L1, but not of SR-BI. In conclusion, bile acids present in the intestinal lumen and the micelles enhance intestinal cholesterol transport into the cell by two different regulatory processes: by reducing the lipid donor size, so that small-size mixed micelles can more easily access brush-border membrane transporters, and by increasing the expression level of the enterocyte NPC1L1. These mechanisms could account for the important inter-individual variations observed in cholesterol intestinal absorption.
引用
收藏
页码:401 / 408
页数:8
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