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PMID: 20307540 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

NPC1L1 and cholesterol transport.

FEBS letters ·Vol. 584 ·No. 13 ·2010-07-02 ·Pages 2740-7

Betters JL, Yu L

Abstract

The polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1), is enriched in the apical membrane of small intestine absorptive enterocytes where it mediates extracellular sterol transport across the brush border membrane. It is essential for intestinal sterol absorption and is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that lowers blood cholesterol in humans. NPC1L1 is also highly expressed in human liver. The hepatic function of NPC1L1 may be to limit excessive biliary cholesterol loss. NPC1L1-dependent sterol uptake seems to be a clathrin-mediated endocytic process and is regulated by cellular cholesterol content. Recently, NPC1L1 inhibition has been shown to have beneficial effects on components of the metabolic syndrome, such as obesity, insulin resistance, and fatty liver, in addition to atherosclerosis.

MeSH Terms
Animals Azetidines/pharmacology Biological Transport/drug effects,physiology Cholesterol/metabolism Ezetimibe Humans Membrane Proteins/genetics,metabolism Membrane Transport Proteins/drug effects,genetics,metabolism Substrate Specificity
Chemicals
Azetidines Membrane Proteins Membrane Transport Proteins NPC1L1 protein, human Npc1l1 protein, mouse Cholesterol Ezetimibe
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Betters Jenna L
Department of Pathology Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA.
Yu Liqing
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Article Info
Journal
FEBS letters
Abbr.
FEBS Lett
ISSN
1873-3468
DOI
10.1016/j.febslet.2010.03.030
Published
2010-07-02
Epub
2010-00-19
Pages
2740-7
Language
English
Region
England
NLM ID
0155157
PMCID
PMC2909875
Subset
IM
Grants
NIDDK NIH HHS · F32 DK084582 · United States
NIDDK NIH HHS · R01 DK085176 · United States
NIDDK NIH HHS · R01 DK085176-01 · United States
NIDDK NIH HHS · 1F32DK084582-01 · United States
External Links
PubMed source DOI: 10.1016/j.febslet.2010.03.030 PMC Full Text View journal details
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