Document Detail


The effects of apolipoprotein F deficiency on high density lipoprotein cholesterol metabolism in mice.
MedLine Citation:
PMID:  22363685     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apolipoprotein F (apoF) is 29 kilodalton secreted sialoglycoprotein that resides on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid Transfer Inhibitor protein (LTIP) based on its ability to inhibit cholesteryl ester transfer protein (CETP)-mediated transfer events between lipoproteins. In contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic alpha helices and its true physiological function remains unknown. We previously showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol levels by 20-25% by accelerating clearance from the circulation. In order to investigate the effect of physiological levels of ApoF expression on HDL cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid or protein composition. Sex-specific differences were observed in hepatic cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO mice had increased liver cholesteryl ester content relative to wild type controls on a chow diet (KO: 3.4+/-0.9 mg/dl vs. WT: 1.2+/-0.3 mg/dl, p<0.05). No differences were observed in ABCG1-mediated cholesterol efflux capacity in either sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT controls.
Authors:
William R Lagor; David W Fields; Sumeet A Khetarpal; Arthi Kumaravel; Wen Lin; Nathaniel Weintraub; Kaijin Wu; Sarah F Hamm-Alvarez; Denise Drazul-Schrader; Margarita de la Llera-Moya; George H Rothblat; Daniel J Rader
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-20
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-02-24     Completed Date:  2012-06-29     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e31616     Citation Subset:  IM    
Affiliation:
Division of Translational Medicine and Human Genetics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. wlagor@mail.med.upenn.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoproteins / deficiency*,  secretion
Biological Transport
Cholesterol, HDL / blood,  metabolism*
Diet, High-Fat
Feeding Behavior
Female
Genes, Reporter
Glycosylation
HEK293 Cells
Humans
Male
Mice
Mice, Knockout
Molecular Weight
Protein Processing, Post-Translational
Staining and Labeling
beta-Galactosidase / metabolism
Grant Support
ID/Acronym/Agency:
P01 HL022633-32/HL/NHLBI NIH HHS; U01HG004080/HG/NHGRI NIH HHS; U01HG004085/HG/NHGRI NIH HHS; U42RR024244/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins; 0/Cholesterol, HDL; 0/apolipoprotein F; EC 3.2.1.23/beta-Galactosidase
Comments/Corrections

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


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