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

• Published in: Journal of lipid research Vol. 47; no. 12; pp. 2631 - 2639
• Main Authors: Dugué-Pujol, Sonia, Rousset, Xavier, Pastier, Danièle, Quang, Nhuan Tran, Pautre, Virginie, Chambaz, Jean, Chabert, Michèle, Kalopissis, Athina-Despina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2006; American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Animals; Apolipoprotein A-II - blood; Apolipoprotein A-II - deficiency; Apolipoprotein A-II - genetics; apolipoprotein A-II knockout mice; chylomicrons; Chylomicrons - metabolism; Female; Humans; Hyperglycemia - blood; Hyperglycemia - etiology; Intestinal Mucosa - metabolism; Lipoproteins - blood; Lipoproteins, VLDL - blood; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; plasma residence time; postprandial hypertriglyceridemia; Recombinant Proteins - blood; Recombinant Proteins - genetics; transgenic mice; Triglycerides - blood; very low density lipoprotein; plasma residence time; very low density lipoprotein; postprandial hypertriglyceridemia; apolipoprotein A-II knockout mice; transgenic mice; chylomicrons
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M600112-JLR200

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.