J. Lipid Res.
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Papers In Press, published online ahead of print December 3, 2007
J. Lipid Res., doi:10.1194/jlr.M700281-JLR200
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Submitted on June 15, 2007
Revised on December 3, 2007
Accepted on December 3, 2007

Effect of apolipoprotein A-V on plasma triglyceride, lipoprotein size and composition in genetically engineered mice

Lisa Nelbach, Xiao Shu, Robert J. Konrad, Robert O. Ryan, and Trudy M. Forte

Children's Hospital Oakland Research Institute, Oakland, CA 94609

Corresponding Author: tforte{at}chori.org

Transgenic mice that overexpress the human APOA5 gene, yet lack an endogenous mouse apoa5 gene (APOA5 Tg mice), were generated. Subsequently, the effect of human apoA-V expression on plasma triglyceride (TG) concentration and lipoprotein and apolipoprotein distribution was determined and compared to mice deficient in apoA-V (apoa5-/- mice). NMR analysis of plasma lipoproteins revealed that APOA5 Tg mice had a very low VLDL concentration (26.4±7.7 nmol/dL) whereas VLDL in apoa5-/- mice was 18-fold higher (467±152 nmol/dL). SDS-PAGE analysis of the d<1.063 g/mL plasma fraction revealed that the apoB-100/B-48 ratio was 14-fold higher in APOA5 Tg vs apoa5-/- mice and apoE/total apoB was 7-fold greater in APOA5 Tg vs apoa5-/- mice. It is anticipated that a reduction in apoB-100/B-48 ratio as well as that for apoE/apoB would impair uptake of VLDL and remnants in apoa5-/- mice, thereby contributing to elevated plasma TG levels. The concentration of apoA-V in APOA5 Tg mice was 12.5±2.9 µg/mL which is approximately 50-100-fold higher than that reported for normolipidemic humans. ApoA-V was predominantly associated with HDL but was rapidly and efficiently redistributed to apoA-V-deficient VLDL upon incubation. Consistent with findings reported for human subjects, apoA-V concentration was positively correlated with TG levels in normolipidemic APOA5 Tg mice. It is conceivable that, in a situation where apoA-V is chronically overexpressed, complex interactions among factors regulating TG homeostasis may result in a positive correlation of apoA-V with TG concentrations.


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X. Shu, R. O. Ryan, and T. M. Forte
Intracellular lipid droplet targeting by apolipoprotein A-V requires the carboxyl-terminal segment
J. Lipid Res., August 1, 2008; 49(8): 1670 - 1676.
[Abstract] [Full Text] [PDF]


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