Document Detail


NPC1L1 and SR-BI are involved in intestinal cholesterol absorption from small-size lipid donors.
MedLine Citation:
PMID:  18373109     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ziad Haikal; Barbara Play; Jean-François Landrier; Annie Giraud; Odette Ghiringhelli; Denis Lairon; Dominique Jourdheuil-Rahmani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-29
Journal Detail:
Title:  Lipids     Volume:  43     ISSN:  0024-4201     ISO Abbreviation:  Lipids     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-22     Completed Date:  2008-09-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0060450     Medline TA:  Lipids     Country:  United States    
Other Details:
Languages:  eng     Pagination:  401-8     Citation Subset:  IM    
Affiliation:
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.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Bile Acids and Salts / physiology
Cell Line
Cholesterol, Dietary / metabolism*
DNA Primers
Gene Expression Regulation / physiology
Humans
Intestinal Absorption / physiology*
Membrane Proteins / genetics,  metabolism,  physiology*
Scavenger Receptors, Class B / genetics,  metabolism,  physiology*
Solubility
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholesterol, Dietary; 0/DNA Primers; 0/Membrane Proteins; 0/NPC1L1 protein, human; 0/SCARB1 protein, human; 0/Scavenger Receptors, Class B

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