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Respective contributions of intestinal Niemann-Pick C1-like 1 and scavenger receptor class B type I to cholesterol and tocopherol uptake: in vivo v. in vitro studies.
- Source :
-
The British journal of nutrition [Br J Nutr] 2012 May; Vol. 107 (9), pp. 1296-304. Date of Electronic Publication: 2011 Sep 20. - Publication Year :
- 2012
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Abstract
- The intestinal absorption of cholesterol and lipid micronutrients such as vitamin E has been shown to share some common pathways. The present study aims to further compare the uptake of cholesterol ([3H]cholesterol v. 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3-ol (NBD-cholesterol)) and tocopherol in Caco-2 TC-7 cells and in mouse intestine, with special focus on the respective roles of scavenger receptor class B type I (SR-BI) and Niemann-Pick C1-like 1 (NPC1L1). Conversely to NBD-cholesterol, the uptakes of [3H]cholesterol and tocopherol by Caco-2 cells were impaired by both block lipid transport-1 and ezetimibe, which inhibit SR-BI and NPC1L1, respectively. These inhibitions occurred only when cholesterol or tocopherol was delivered to cells included in micelles that contained biliary acid and at least oleic acid as a lipid. In vivo, after 2 h of digestion in mice, the uptake of the two cholesterol analogues and of tocopherol all showed distinct patterns along the duodenum-jejunum axis. [3H]Cholesterol uptake, which correlated closely to NPC1L1 mRNA expression in wild-type (wt) mice, was strongly inhibited by ezetimibe. Intestinal SR-BI overexpression did not change NPC1L1 expression and led to a significant increase in [3H]cholesterol uptake in the distal jejunum. Conversely, neither ezetimibe treatment nor SR-BI overexpression had an effect on NBD-cholesterol uptake. However, in contrast with SR-BI mRNA expression, tocopherol absorption increased strongly up to the distal jejunum in wt mice where it was specifically inhibited by ezetimibe, and was increased in the proximal intestine of intestinal SR-BI-overexpressing mice. Thus, cholesterol and tocopherol uptakes share common pathways in cell culture models, but display different in vivo absorption patterns associated with distinct contributions of SR-BI and NPC1L1.
- Subjects :
- 4-Chloro-7-nitrobenzofurazan metabolism
Absorption
Animals
Azetidines pharmacology
Bile Acids and Salts metabolism
Caco-2 Cells
Cell Membrane metabolism
Cholesterol metabolism
Chromatography, High Pressure Liquid
Cyclopentanes pharmacology
Duodenum metabolism
Ezetimibe
Gene Expression Profiling
Humans
Jejunum metabolism
Lipid Metabolism
Mice
Mice, Inbred C57BL
Micelles
Thiosemicarbazones pharmacology
Time Factors
Vitamin E metabolism
4-Chloro-7-nitrobenzofurazan analogs & derivatives
Cholesterol analogs & derivatives
Gene Expression Regulation
Membrane Transport Proteins physiology
Scavenger Receptors, Class B physiology
gamma-Tocopherol metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2662
- Volume :
- 107
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The British journal of nutrition
- Publication Type :
- Academic Journal
- Accession number :
- 21929836
- Full Text :
- https://doi.org/10.1017/S0007114511004405