Linked Life Data

8864964

Source:http://linkedlifedata.com/resource/pubmed/id/8864964

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1997-1-23
pubmed:abstractText
We previously showed that human apoC-III expression in transgenic mice causes hypertriglyceridemia due to the accumulation of enlarged very low density lipoprotein (VLDL)-like particles, with increased triglycerides and apoC-III and decreased apoE. In vivo turnover studies indicated the metabolic basis was decreased particle fractional catabolic rate. The presence of enlarged triglyceride-rich particles with prolonged residence time in plasma implied defective lipolysis, but in vitro these particles were good substrates for purified lipoprotein lipase (LPL). In the current study we further characterize the metabolic properties of these particles. We show that expression of a mouse apoC-III transgene can also cause hypertriglyceridemia with a similar accumulation of a VLDL-like particle with increased apoC-III and decreased apoE. A vitamin A fat tolerance test was used to show that MoCIIITg and HuCIIITg mice had similarly delayed clearance of triglyceride-rich postprandial particles. Thus, the previously observed hypertriglyceridemia caused by human apoC-III transgene expression was not due interspecies incompatibility but a property of apoC-III. In further experiments we showed VLDL from apoC-III transgenic mice interacted poorly with fibroblast lipoprotein receptors and this could be corrected by adding exogenous apoE. In addition, control VLDL interaction could be decreased by exogenous apoC-III. Moreover, the hypertriglyceridemia of HuCIIITg mice could be normalized by crossbreeding with HuETg mice. Thus, a functionally significant reciprocal relationship of apoC-III and apoE exists, presumably due to competition for space on the surface of triglyceride-rich lipoproteins. Finally, VLDL from HuCIITg and MoCIIITg mice showed decreased binding to heparin-Sepharose. This suggests and additional locus of the defect in these mice could potentially be in the binding of triglyceride-rich lipoproteins to heparan sulfate proteoglycan matrix on the surface of endothelial cells in which LPL is embedded. This could explain the predicted functional lipase deficiency in apoC-III transgenic mice based on the observation of a prolonged residence time of enlarged triglyceride-rich lipoproteins.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1802-11
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8864964-Animals, pubmed-meshheading:8864964-Apolipoprotein C-III, pubmed-meshheading:8864964-Apolipoproteins C, pubmed-meshheading:8864964-Dietary Fats, pubmed-meshheading:8864964-Fasting, pubmed-meshheading:8864964-Fibroblasts, pubmed-meshheading:8864964-Gene Expression Regulation, pubmed-meshheading:8864964-Humans, pubmed-meshheading:8864964-Hypertriglyceridemia, pubmed-meshheading:8864964-Lipids, pubmed-meshheading:8864964-Lipoproteins, VLDL, pubmed-meshheading:8864964-Male, pubmed-meshheading:8864964-Mice, pubmed-meshheading:8864964-Mice, Transgenic, pubmed-meshheading:8864964-Postprandial Period, pubmed-meshheading:8864964-RNA, Messenger, pubmed-meshheading:8864964-Time Factors, pubmed-meshheading:8864964-Transgenes, pubmed-meshheading:8864964-Triglycerides, pubmed-meshheading:8864964-Vitamin A
pubmed:year
1996
pubmed:articleTitle
Further characterization of the metabolic properties of triglyceride-rich lipoproteins from human and mouse apoC-III transgenic mice.
pubmed:affiliation
Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY 10021-6399, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.