Publication Date:
2004-02-21
Description:
Dietary cholesterol consumption and intestinal cholesterol absorption contribute to plasma cholesterol levels, a risk factor for coronary heart disease. The molecular mechanism of sterol uptake from the lumen of the small intestine is poorly defined. We show that Niemann-Pick C1 Like 1(NPC1L1) protein plays a critical role in the absorption of intestinal cholesterol. NPC1L1 expression is enriched in the small intestine and is in the brush border membrane of enterocytes. Although otherwise phenotypically normal, NPC1L1-deficient mice exhibit a substantial reduction in absorbed cholesterol, which is unaffected by dietary supplementation of bile acids. Ezetimibe, a drug that inhibits cholesterol absorption, had no effect in NPC1L1 knockout mice, suggesting that NPC1L1 resides in an ezetimibe-sensitive pathway responsible for intestinal cholesterol absorption.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Altmann, Scott W -- Davis, Harry R Jr -- Zhu, Li-Ji -- Yao, Xiaorui -- Hoos, Lizbeth M -- Tetzloff, Glen -- Iyer, Sai Prasad N -- Maguire, Maureen -- Golovko, Andrei -- Zeng, Ming -- Wang, Luquan -- Murgolo, Nicholas -- Graziano, Michael P -- New York, N.Y. -- Science. 2004 Feb 20;303(5661):1201-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiovascular/Endocrine Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ, 07033-0539, USA. scott.altmann@spcorp.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14976318" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Anticholesteremic Agents/pharmacology
;
Azetidines/pharmacology
;
Cholesterol/*metabolism
;
Cholesterol, Dietary/*metabolism
;
Cholic Acid/administration & dosage/pharmacology
;
Computational Biology
;
Enterocytes/*metabolism
;
Ezetimibe
;
Female
;
Gene Expression Profiling
;
Humans
;
*Intestinal Absorption/drug effects
;
Intestine, Small/metabolism
;
Jejunum/metabolism
;
Liver/metabolism
;
Male
;
Membrane Proteins/chemistry/genetics/*metabolism
;
Membrane Transport Proteins/chemistry/genetics/*metabolism
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Molecular Sequence Data
;
Oligonucleotide Array Sequence Analysis
;
Proteins/chemistry/genetics/*metabolism
;
Rats
;
Rats, Sprague-Dawley
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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