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A more recent version of this article appeared on December 1, 2006

Papers In Press, published online ahead of print September 21, 2006
J. Lipid Res., doi:10.1194/jlr.M600112-JLR200
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Submitted on March 7, 2006
Revised on September 12, 2006
Accepted on September 20, 2006

Human apolipoprotein A-II induces hypertriglyceridemia in transgenic mice by associating with triglyceride-rich lipoproteins in plasma and impairing their catabolism

Sonia Dugué-Pujol, Xavier Rousset, Danièle Pastier, Nhuan Tran Quang, Virginie Pautre, Jean Chambaz, Michèle Chabert, and Athina-Despina Kalopissis

Inserm UMR505 and Université Pierre et Marie Curie, Centre de Recherche des Cordeliers, Paris 75006

Corresponding Author: athina.kalopissis-u505{at}bhdc.jussieu.fr

Postprandial hypertriglyceridemia and low plasma HDL levels that are principal features of the metabolic syndrome, are displayed by transgenic mice expressing human apolipoprotein A-II (hapo A-II). In these mice hypertriglyceridemia results from inhibition of lipoprotein lipase and hepatic lipase activities by hapo A-II carried on VLDL. This study aimed to determine whether the association of hapo A-II with triglyceride-rich lipoproteins (TRL) is sufficient to impair their catabolism. To measure plasma TRL residence time, intestinal TRL production was induced by a radioactive oral lipid bolus. Radioactive and total triglyceride (TG) were rapidly cleared in control mice but accumulated in plasma of transgenic mice, in relation to hapo A-II concentration. Similar plasma TG accumulations were measured in transgenic mice with or without endogenous apo A-II expression. Human apo A-II (synthesized in liver) was detected in chylomicrons (produced by intestine). The association of hapo A-II with TRL in plasma was further confirmed by the absence of hapo A-II in chylomicrons and VLDL of transgenic mice injected with Triton WR 1339, which prevents apolipoprotein exchanges. We show that the association of hapo A-II with TRL occurs in the circulation and induces postprandial hypertriglyceridemia.


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