Document Detail


Apolipoprotein CI causes hypertriglyceridemia independent of the very-low-density lipoprotein receptor and apolipoprotein CIII in mice.
MedLine Citation:
PMID:  16478678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have recently shown that the predominant hypertriglyceridemia in human apolipoprotein C1 (APOC1) transgenic mice is mainly explained by apoCI-mediated inhibition of the lipoprotein lipase (LPL)-dependent triglyceride (TG)-hydrolysis pathway. Since the very-low-density lipoprotein receptor (VLDLr) and apoCIII are potent modifiers of LPL activity, our current aim was to study whether the lipolysis-inhibiting action of apoCI would be dependent on the presence of the VLDLr and apoCIII in vivo. Hereto, we employed liver-specific expression of human apoCI by using a novel recombinant adenovirus (AdAPOC1). In wild-type mice, moderate apoCI expression leading to plasma human apoCI levels of 12-33 mg/dl dose-dependently and specifically increased plasma TG (up to 6.6-fold, P < 0.001), yielding the same hypertriglyceridemic phenotype as observed in human APOC1 transgenic mice. AdAPOC1 still increased plasma TG in vldlr(-/-) mice (4.1-fold, P < 0.001) and in apoc3(-/-) mice (6.8-fold, P < 0.001) that were also deficient for the low-density lipoprotein receptor (LDLr) and LDLr-related protein (LRP) or apoE, respectively. Thus, irrespective of receptor-mediated remnant clearance by the liver, liver-specific expression of human apoCI causes hypertriglyceridemia in the absence of the VLDLr and apoCIII. We conclude that apoCI is a powerful and direct inhibitor of LPL activity independent of the VLDLr and apoCIII.
Authors:
Caroline C van der Hoogt; Jimmy F P Berbée; Sonia M S Espirito Santo; Gery Gerritsen; Yvonne D Krom; André van der Zee; Louis M Havekes; Ko Willems van Dijk; Patrick C N Rensen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-01-27
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1761     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-04-17     Completed Date:  2006-05-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  213-20     Citation Subset:  IM    
Affiliation:
The Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands. C.C.van_der_Hoogt@lumc.nl
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoprotein C-I
Apolipoprotein C-III
Apolipoproteins C / deficiency,  genetics,  metabolism*
Apolipoproteins E / deficiency,  genetics
Base Sequence
Humans
Hypertriglyceridemia / blood,  etiology*,  genetics,  metabolism*
LDL-Receptor Related Proteins / deficiency,  genetics
Lipids / blood
Lipoprotein Lipase / antagonists & inhibitors,  metabolism
Liver / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Phenotype
RNA, Messenger / genetics,  metabolism
Receptors, LDL / deficiency,  genetics,  metabolism*
Recombinant Proteins / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Apolipoprotein C-I; 0/Apolipoprotein C-III; 0/Apolipoproteins C; 0/Apolipoproteins E; 0/LDL-Receptor Related Proteins; 0/Lipids; 0/RNA, Messenger; 0/Receptors, LDL; 0/Recombinant Proteins; 0/VLDL receptor; EC 3.1.1.34/Lipoprotein Lipase

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


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