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

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, hyper- triglyceridemia results from the inhibition of lipoprotein lipase and hepatic lipase activities by hapoA-II carried on VLDL. This study aimed to determine whether the associa- tion 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 tri- glyceride (TG) were rapidly cleared in control mice but ac- cumulated in plasma of transgenic mice, in relation to hapoA-II concentration. Similar plasma TG accumulations were measured in transgenic mice with or without endoge- nous 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 circula- tion and induces postprandial hypertriglyceridemia.— Dugue´-Pujol, S., X. Rousset, D. Pastier, N. T. Quang, V. Pautre, J. Chambaz, M. Chabert, and A-D. Kalopissis. Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism. J. Lipid Res. 2006. 47: 2631-2639.