Document Detail


Biliary sterol secretion is not required for macrophage reverse cholesterol transport.
MedLine Citation:
PMID:  20620999     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent evidence suggests that the intestine may play a direct facilitative role in reverse cholesterol transport (RCT), independent of hepatobiliary secretion. In order to understand the nonbiliary pathway for RCT, we created both genetic and surgical models of biliary cholesterol insufficiency. To genetically inhibit biliary cholesterol secretion, we generated mice in which Niemann-Pick C1-Like 1 (NPC1L1) was overexpressed in the liver. Compared to controls, NPC1L1(Liver-Tg) mice exhibit a >90% decrease in biliary cholesterol secretion, yet mass fecal sterol loss and macrophage RCT are normal. To surgically inhibit biliary emptying into the intestine, we have established an acute biliary diversion model. Strikingly, macrophage RCT persists in mice surgically lacking the ability to secrete bile into the intestine. Collectively, these studies demonstrate that mass fecal sterol loss and macrophage RCT can proceed in the absence of biliary sterol secretion, challenging the obligate role of bile in RCT.
Authors:
Ryan E Temel; Janet K Sawyer; Liqing Yu; Caleb Lord; Chiara Degirolamo; Allison McDaniel; Stephanie Marshall; Nanping Wang; Ramesh Shah; Lawrence L Rudel; J Mark Brown
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  12     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-12     Completed Date:  2010-10-25     Revised Date:  2012-01-25    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  96-102     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Section on Lipid Sciences, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biliary Tract / metabolism*
Biological Transport
Cholesterol / metabolism*
Liver / metabolism
Macrophages / immunology,  metabolism*
Membrane Transport Proteins / genetics,  metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Models, Animal
Sterols / metabolism*
Grant Support
ID/Acronym/Agency:
1K99-HL096166/HL/NHLBI NIH HHS; 5P01HL049373/HL/NHLBI NIH HHS; K99 HL096166-02/HL/NHLBI NIH HHS; P01 HL049373-18/HL/NHLBI NIH HHS; R00 HL096166-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Transport Proteins; 0/Npc1l1 protein, mouse; 0/Sterols; 57-88-5/Cholesterol
Comments/Corrections

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