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Journal of Lipid Research, Vol. 47, 2631-2639, December 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism

Sonia Dugué-Pujol, Xavier Rousset, Danièle Pastier, Nhuan Tran Quang, Virginie Pautre, Jean Chambaz, Michèle Chabert and Athina-Despina Kalopissis¹

Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 505, Paris, F-75006 France; and Université Pierre et Marie Curie, Paris, F-75006 France

Published, JLR Papers in Press, September 21, 2006.

¹ To whom correspondence should be addressed. e-mail: athina.kalopissis-u505{at}bhdc.jussieu.fr

Postprandial hypertriglyceridemia and low plasma HDL levels, which are principal features of the metabolic syndrome, are displayed by transgenic mice expressing human apolipoprotein A-II (hapoA-II). In these mice, hypertriglyceridemia results from the inhibition of lipoprotein lipase and hepatic lipase activities by hapoA-II carried on VLDL. This study aimed to determine whether the association of hapoA-II with triglyceride-rich lipoproteins (TRLs) 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 hapoA-II concentration. Similar plasma TG accumulations were measured in transgenic mice with or without endogenous apoA-II expression. HapoA-II (synthesized in liver) was detected in chylomicrons (produced by intestine). The association of hapoA-II with TRL in plasma was further confirmed by the absence of hapoA-II in chylomicrons and VLDL of transgenic mice injected with Triton WR 1339, which prevents apolipoprotein exchanges. We show that the association of hapoA-II with TRL occurs in the circulation and induces postprandial hypertriglyceridemia.

Supplementary key words postprandial hypertriglyceridemia • transgenic mice • apolipoprotein A-II knockout mice • chylomicrons • very low density lipoprotein • plasma residence time

Abbreviations: hapoA-II, human apolipoprotein A-II; KO, knockout; mapoA-II, murine apolipoprotein A-II; TG, triglyceride; TRL, triglyceride-rich lipoprotein

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