NPC1L1 and SR-BI are involved in intestinal cholesterol absorption from small-size lipid donors - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Lipids Year : 2008

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

Abstract

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

Dates and versions

hal-02661465 , version 1 (30-05-2020)

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Ziad Haikal, Barbara Play, Jean-Francois Landrier, Annie Giraud, Odette Ghiringhelli, et al.. NPC1L1 and SR-BI are involved in intestinal cholesterol absorption from small-size lipid donors. Lipids, 2008, 43 (5), pp.401-408. ⟨10.1007/s11745-008-3172-7⟩. ⟨hal-02661465⟩
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