Document Detail


ApoE promotes hepatic selective uptake but not RCT due to increased ABCA1-mediated cholesterol efflux to plasma.
MedLine Citation:
PMID:  22383685     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ApoE plays an important role in lipoprotein metabolism. This study investigated the effects of adenovirus-mediated human apoE overexpression (AdhApoE3) on sterol metabolism and in vivo reverse cholesterol transport (RCT). In wild-type mice, AdhApoE3 resulted in decreased HDL cholesterol levels and a shift toward larger HDL in plasma, whereas hepatic cholesterol content increased (P < 0.05). These effects were dependent on scavenger receptor class B type I (SR-BI) as confirmed using SR-BI-deficient mice. Kinetic studies demonstrated increased plasma HDL cholesteryl ester catabolic rates (P < 0.05) and higher hepatic selective uptake of HDL cholesteryl esters in AdhApoE3-injected wild-type mice (P < 0.01). However, biliary and fecal sterol output as well as in vivo macrophage-to-feces RCT studied with (3)H-cholesterol-loaded mouse macrophage foam cells remained unchanged upon human apoE overexpression. Similar results were obtained using hApoE3 overexpression in human CETP transgenic mice. However, blocking ABCA1-mediated cholesterol efflux from hepatocytes in AdhApoE3-injected mice using probucol increased biliary cholesterol secretion (P < 0.05), fecal neutral sterol excretion (P < 0.05), and in vivo RCT (P < 0.01), specifically within neutral sterols. These combined data demonstrate that systemic apoE overexpression increases i) SR-BI-mediated selective uptake into the liver and ii) ABCA1-mediated efflux of RCT-relevant cholesterol from hepatocytes back to the plasma compartment, thereby resulting in unchanged fecal mass sterol excretion and overall in vivo RCT.
Authors:
Wijtske Annema; Arne Dikkers; Jan Freark de Boer; Thomas Gautier; Patrick C N Rensen; Daniel J Rader; Uwe J F Tietge
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-01
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-12     Completed Date:  2012-08-08     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  929-40     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / metabolism*
Animals
Antigens, CD36 / metabolism
Apolipoprotein E3 / genetics,  metabolism*
Biliary Tract / drug effects,  secretion
Biological Transport / drug effects
Cholesterol / blood*,  metabolism*,  secretion
Cholesterol, HDL / chemistry,  metabolism*
Feces
Hepatocytes / drug effects,  metabolism
Humans
Liver / cytology,  drug effects,  metabolism*
Macrophages / drug effects,  metabolism
Mice
Mice, Inbred C57BL
Particle Size
Probucol / pharmacology
Grant Support
ID/Acronym/Agency:
HL022633/HL/NHLBI NIH HHS; HL059407/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/ATP binding cassette transporter 1; 0/Antigens, CD36; 0/Apolipoprotein E3; 0/Cholesterol, HDL; 23288-49-5/Probucol; 57-88-5/Cholesterol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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