Source:http://linkedlifedata.com/resource/pubmed/id/10585451
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
50
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| pubmed:dateCreated |
2000-1-13
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| pubmed:abstractText |
ApoE-deficient mice on low fat diet show hepatic triglyceride accumulation and a reduced very low density lipoprotein (VLDL) triglyceride production rate. To establish the role of apoE in the regulation of hepatic VLDL production, the human APOE3 gene was introduced into apoE-deficient mice by cross-breeding with APOE3 transgenics (APOE3/apoe-/- mice) or by adenoviral transduction. APOE3 was expressed in the liver and, to a lesser extent, in brain, spleen, and lung of transgenic APOE3/apoe-/- mice similar to endogenous apoe. Plasma cholesterol levels in APOE/apoe-/- mice (3.4 +/- 0.5 mM) were reduced when compared with apoe-/- mice (12.6 +/- 1.4 mM) but still elevated when compared with wild type control values (1.9 +/- 0.1 mM). Hepatic triglyceride accumulation in apoE-deficient mice was completely reversed by introduction of the APOE3 transgene. The in vivo hepatic VLDL-triglyceride production rate was reduced to 36% of control values in apoE-deficient mice but normalized in APOE3/apoe-/- mice. Hepatic secretion of apoB was not affected in either of the strains. Secretion of (3)H-labeled triglycerides synthesized from [(3)H]glycerol by cultured hepatocytes from apoE-deficient mice was four times lower than by APOE3/apoe-/- or control hepatocytes. The average size of secreted VLDL particles produced by cultured apoE-deficient hepatocytes was significantly reduced when compared with those of APOE3/apoe-/- and wild type mice. Hepatic expression of human APOE3 cDNA via adenovirus-mediated gene transfer in apoE-deficient mice resulted in a reduction of plasma cholesterol depending on plasma apoE3 levels. The in vivo VLDL-triglyceride production rate in these mice was increased up to 500% compared with LacZ-injected controls and correlated with the amount of apoE3 per particle. These findings indicate a regulatory role of apoE in hepatic VLDL-triglyceride secretion, independent from its role in lipoprotein clearance.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins E,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Nonesterified,
http://linkedlifedata.com/resource/pubmed/chemical/Glycerol,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, VLDL,
http://linkedlifedata.com/resource/pubmed/chemical/Phytosterols,
http://linkedlifedata.com/resource/pubmed/chemical/Sitosterols,
http://linkedlifedata.com/resource/pubmed/chemical/Sterols,
http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/campesterol,
http://linkedlifedata.com/resource/pubmed/chemical/lathosterol,
http://linkedlifedata.com/resource/pubmed/chemical/sitosterol,
http://linkedlifedata.com/resource/pubmed/chemical/very low density lipoprotein...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
10
|
| pubmed:volume |
274
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
35711-8
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10585451-Animals,
pubmed-meshheading:10585451-Apolipoproteins E,
pubmed-meshheading:10585451-Cells, Cultured,
pubmed-meshheading:10585451-Cholesterol,
pubmed-meshheading:10585451-Crosses, Genetic,
pubmed-meshheading:10585451-Fatty Acids, Nonesterified,
pubmed-meshheading:10585451-Glycerol,
pubmed-meshheading:10585451-Homeostasis,
pubmed-meshheading:10585451-Humans,
pubmed-meshheading:10585451-Lipoproteins,
pubmed-meshheading:10585451-Lipoproteins, VLDL,
pubmed-meshheading:10585451-Liver,
pubmed-meshheading:10585451-Mice,
pubmed-meshheading:10585451-Mice, Knockout,
pubmed-meshheading:10585451-Mice, Transgenic,
pubmed-meshheading:10585451-Microscopy, Immunoelectron,
pubmed-meshheading:10585451-Phytosterols,
pubmed-meshheading:10585451-Sitosterols,
pubmed-meshheading:10585451-Sterols,
pubmed-meshheading:10585451-Triglycerides,
pubmed-meshheading:10585451-Tritium
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| pubmed:year |
1999
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| pubmed:articleTitle |
Apolipoprotein E participates in the regulation of very low density lipoprotein-triglyceride secretion by the liver.
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| pubmed:affiliation |
Groningen Institute for Drug Studies, University Hospital Groningen, 9713 GZ Groningen.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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