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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2006-4-17
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoprotein C-I,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoprotein C-III,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins C,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins E,
http://linkedlifedata.com/resource/pubmed/chemical/LDL-Receptor Related Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoprotein Lipase,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/VLDL receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-3002
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
1761
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
213-20
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16478678-Animals,
pubmed-meshheading:16478678-Apolipoprotein C-I,
pubmed-meshheading:16478678-Apolipoprotein C-III,
pubmed-meshheading:16478678-Apolipoproteins C,
pubmed-meshheading:16478678-Apolipoproteins E,
pubmed-meshheading:16478678-Base Sequence,
pubmed-meshheading:16478678-Humans,
pubmed-meshheading:16478678-Hypertriglyceridemia,
pubmed-meshheading:16478678-LDL-Receptor Related Proteins,
pubmed-meshheading:16478678-Lipids,
pubmed-meshheading:16478678-Lipoprotein Lipase,
pubmed-meshheading:16478678-Liver,
pubmed-meshheading:16478678-Mice,
pubmed-meshheading:16478678-Mice, Inbred C57BL,
pubmed-meshheading:16478678-Mice, Knockout,
pubmed-meshheading:16478678-Mice, Transgenic,
pubmed-meshheading:16478678-Phenotype,
pubmed-meshheading:16478678-RNA, Messenger,
pubmed-meshheading:16478678-Receptors, LDL,
pubmed-meshheading:16478678-Recombinant Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Apolipoprotein CI causes hypertriglyceridemia independent of the very-low-density lipoprotein receptor and apolipoprotein CIII in mice.
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pubmed: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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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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