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.
机构:
Univ Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, Japan
Yamanashi, Yoshihide
Takada, Tappei
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h-index: 0
机构:
Univ Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, Japan
Takada, Tappei
Suzuki, Hiroshi
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, Japan
机构:
Univ Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, Japan
Yamanashi, Yoshihide
Takada, Tappei
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, Japan
Takada, Tappei
Suzuki, Hiroshi
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, JapanUniv Tokyo, Tokyo Univ Hosp, Dept Pharm, Fac Med,Bunkyo Ku, Tokyo 1138655, Japan