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, 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.
Dugué-Pujol
Sonia
S
Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 505, Paris, F-75006 France.
Rousset
Xavier
X
Pastier
Danièle
D
Quang
Nhuan Tran
NT
Pautre
Virginie
V
Chambaz
Jean
J
Chabert
Michèle
M
Kalopissis
Athina-Despina
AD
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*
D016633:Apolipoprotein A-II; D002914:Chylomicrons; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D011994:Recombinant Proteins; D014280:Triglycerides