Document Detail


Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport.
MedLine Citation:
PMID:  20809793     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increased blood cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It functions as a sterol transporter to mediate intestinal cholesterol absorption and counter-balances hepatobiliary cholesterol excretion. NPC1L1 is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that is widely used in treating hypercholesterolemia. Recent findings suggest that NPC1L1 deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis and obesity in addition to reducing blood cholesterol. Future studies should focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport and elucidation of how a cholesterol transporter modulates the pathogenesis of metabolic diseases.
Authors:
Lin Jia; Jenna L Betters; Liqing Yu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Annual review of physiology     Volume:  73     ISSN:  1545-1585     ISO Abbreviation:  Annu. Rev. Physiol.     Publication Date:  2011  
Date Detail:
Created Date:  2011-02-14     Completed Date:  2011-07-08     Revised Date:  2012-03-22    
Medline Journal Info:
Nlm Unique ID:  0370600     Medline TA:  Annu Rev Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  239-59     Citation Subset:  IM    
Affiliation:
Section on Lipid Sciences, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticholesteremic Agents / pharmacology
Atherosclerosis / drug therapy,  metabolism
Azetidines / pharmacology
Biliary Tract / drug effects,  metabolism
Biological Transport / drug effects,  physiology
Carrier Proteins / metabolism*
Cholesterol / metabolism*
Endocytosis / drug effects,  physiology
Fatty Liver / drug therapy,  metabolism
Humans
Intestinal Absorption / drug effects,  physiology
Intestines / drug effects,  metabolism*
Liver / drug effects,  metabolism*
Membrane Proteins / genetics,  metabolism*
Mice
Obesity / drug therapy,  metabolism
Phytosterols / metabolism
Primates / metabolism
Grant Support
ID/Acronym/Agency:
1F32DK084582-01/DK/NIDDK NIH HHS; R01DK085176/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Azetidines; 0/Carrier Proteins; 0/Membrane Proteins; 0/NPC1L1 protein, human; 0/Phytosterols; 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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