Apolipoprotein Ci Causes Hypertriglyceridemia Independent of the Very-low-density Lipoprotein Receptor and Apolipoprotein Ciii in Mice.
From: 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
Biochimica et biophysica acta
- Publish Date: Feb 2006
- ISSN: 0006-3002
- Volume: 1761
- Issue: 2
- Pages: 213-20
- Medium: Print
- Language: English
- Citation (JAMA): van der Hoogt Caroline C, Berbée Jimmy F P, Espirito Santo Sonia M S, et al. Apolipoprotein Ci Causes Hypertriglyceridemia Independent of the Very-low-density Lipoprotein Receptor and Apolipoprotein Ciii in Mice.. Biochim. Biophys. Acta Feb 2006;1761:213-20
Abstract
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.
Mesh Headings (Keywords): Animals, Apolipoprotein C-I, Apolipoprotein C-III, Apolipoproteins C, Apolipoproteins E, Base Sequence, Humans, Hypertriglyceridemia, LDL-Receptor Related Proteins, Lipids, Lipoprotein Lipase, Liver, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Phenotype, RNA, Messenger, Receptors, LDL, Recombinant Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16478678
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