NPC1L1 and SR-BI are involved in intestinal cholesterol absorption from small-size lipid donors.
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 (<or=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.
Haikal
Ziad
Z
INRA, UMR1260 Nutriments Lipidiques et Prévention des Maladies Métaboliques, INSERM, U476, Univ Aix-Marseille 1, Univ Aix-Marseille 2, Faculté de Médecine, IPHM-IFR 125, 27 bld Jean Moulin, 13385 Marseille, France.
Play
Barbara
B
Landrier
Jean-François
JF
Giraud
Annie
A
Ghiringhelli
Odette
O
Lairon
Denis
D
Jourdheuil-Rahmani
Dominique
D
D001483:Base Sequence; D001647:Bile Acids and Salts / Q000502:physiology; D002460:Cell Line; D002791:Cholesterol, Dietary / Q000378:metabolism*; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D026901:Membrane Transport Proteins; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012995:Solubility
D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D017931:DNA Primers; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B