title: Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 505, Paris, F-75006 France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Dugué-Pujol
authors.forename: Xavier
authors.initials: X
authors.lastname: Rousset
authors.forename: Danièle
authors.initials: D
authors.lastname: Pastier
authors.forename: Nhuan Tran
authors.initials: NT
authors.lastname: Quang
authors.forename: Virginie
authors.initials: V
authors.lastname: Pautre
authors.forename: Jean
authors.initials: J
authors.lastname: Chambaz
authors.forename: Michèle
authors.initials: M
authors.lastname: Chabert
authors.forename: Athina-Despina
authors.initials: AD
authors.lastname: Kalopissis
mesh_terms: D000818:Animals; D016633:Apolipoprotein A-II / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D002914:Chylomicrons / Q000378:metabolism; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology; D007413:Intestinal Mucosa / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics; D014280:Triglycerides / Q000097:blood*
chemical_list: D016633:Apolipoprotein A-II; D002914:Chylomicrons; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D011994:Recombinant Proteins; D014280:Triglycerides