| Use of NBD-cholesterol to identify a minor but NPC1L1-independent cholesterol absorption pathway in mouse intestine. | |
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MedLine Citation:
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PMID: 21071508 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The importance of Niemann-Pick C1 Like-1 (NPC1L1) protein in intestinal absorption of dietary sterols, including both cholesterol and phytosterols, is well documented. However, the exact mechanism by which NPC1L1 facilitates cholesterol transport remains controversial. This study administered 22-(N(-7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol) and [(3)H]cholesterol to Npc1l1(+/+) and Npc1l1(-/-) mice to determine whether NPC1L1 facilitates dietary sterol uptake by enterocytes and/or participates in intracellular sterol delivery to the endoplasmic reticulum (ER) for lipoprotein assembly before secretion into plasma circulation. Results showed that [(3)H]cholesterol absorption was reduced but not abolished in Npc1l1(-/-) mice compared with Npc1l1(+/+) mice. In the presence of Pluronic L-81 to block pre-chylomicron exit from the ER, significant amounts of [(3)H]cholesterol were found to be associated with lipid droplets in the intestinal mucosa of both Npc1l1(+/+) and Npc1l1(-/-) mice, and the intracellular [(3)H]cholesterol can be esterified to cholesteryl esters. These results provided evidence indicating that the main function of NPC1L1 is to promote cholesterol uptake from the intestinal lumen but that it is not necessary for intracellular cholesterol transport to the ER. Surprisingly, NBD-cholesterol was taken up by intestinal mucosa, esterified to NBD-cholesteryl esters, and transported to plasma circulation to similar extent between Npc1l1(+/+) and Npc1l1(-/-) mice. Ezetimibe treatment also had no impact on NBD-cholesterol absorption by Npc1l1(+/+) mice. Thus, NBD-cholesterol absorption proceeds through an NPC1L1-independent and ezetimibe-insensitive sterol absorption mechanism. Taken together, these results indicate that NBD-cholesterol can be used to trace the alternative cholesterol absorption pathway but is not suitable for tracking NPC1L1-mediated cholesterol absorption. |
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Authors:
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Michelle R Adams; Eddy Konaniah; James G Cash; David Y Hui |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-11 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 300 ISSN: 1522-1547 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-30 Completed Date: 2011-02-01 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G164-9 Citation Subset: IM |
Affiliation:
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Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, Cincinnati, Ohio 45237, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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4-Chloro-7-nitrobenzofurazan
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analogs & derivatives Animals Azetidines / pharmacology Cholesterol / analogs & derivatives, metabolism* Cholesterol, Dietary / metabolism Intestinal Absorption / drug effects* Membrane Transport Proteins / physiology* Mice Niemann-Pick Diseases / metabolism Poloxamer / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK-076907/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/7-nitrobenz-2-oxa-1,3-diazol-4-ylcholesterol; 0/Azetidines; 0/Cholesterol, Dietary; 0/Membrane Transport Proteins; 0/Npc1l1 protein, mouse; 10199-89-0/4-Chloro-7-nitrobenzofurazan; 106392-12-5/Poloxamer; 163222-33-1/ezetimibe; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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