Niemann-Pick C1 Like 1 Protein Is Critical for Intestinal Cholesterol Absorption
Top Cited Papers
- 20 February 2004
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 303 (5661) , 1201-1204
- https://doi.org/10.1126/science.1093131
Abstract
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 C1Like 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.Keywords
This publication has 30 references indexed in Scilit:
- Stimulation of Cholesterol Excretion by the Liver X Receptor Agonist Requires ATP-binding Cassette Transporters G5 and G8Journal of Biological Chemistry, 2003
- Synthesis of iodinated biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitorsBioorganic & Medicinal Chemistry Letters, 2002
- Disruption of the Sterol 27-Hydroxylase Gene in Mice Results in Hepatomegaly and HypertriglyceridemiaJournal of Biological Chemistry, 2000
- Accumulation of Dietary Cholesterol in Sitosterolemia Caused by Mutations in Adjacent ABC TransportersScience, 2000
- Evidence for a Niemann–Pick C (NPC) Gene Family: Identification and Characterization of NPC1L1Genomics, 2000
- Discovery of 1-(4-Fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)- hydroxypropyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone (SCH 58235): A Designed, Potent, Orally Active Inhibitor of Cholesterol AbsorptionJournal of Medicinal Chemistry, 1998
- Niemann-Pick C1 Disease Gene: Homology to Mediators of Cholesterol HomeostasisScience, 1997
- Human Homolog of patched , a Candidate Gene for the Basal Cell Nevus SyndromeScience, 1996
- Nucleotide sequence of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, a glycoprotein of endoplasmic reticulumNature, 1984
- Absorption and Metabolism of Dietary CholesterolAnnual Review of Nutrition, 1983