Human apolipoprotein A-II determines plasma triglycerides by regulating lipoprotein lipase activity and high-density lipoprotein proteome.
BACKGROUND
Apolipoprotein (apo) A-II is the second most abundant high-density lipoprotein (HDL) apolipoprotein. We assessed the mechanism involved in the altered postprandial triglyceride-rich lipoprotein metabolism of female human apoA-II-transgenic mice (hapoA-II-Tg mice), which results in up to an 11-fold increase in plasma triglyceride concentration. The relationships between apoA-II, HDL composition, and lipoprotein lipase (LPL) activity were also analyzed in a group of normolipidemic women.


RESULTS
Triglyceride-rich lipoprotein catabolism was decreased in hapoA-II-Tg mice compared to control mice. This suggests that hapoA-II, which was mainly associated with HDL during fasting and postprandially, impairs triglyceride-rich lipoprotein lipolysis. HDL isolated from hapoA-II-Tg mice impaired bovine LPL activity. Two-dimensional gel electrophoresis, mass spectrometry, and immunonephelometry identified a marked deficiency in the HDL content of apoA-I, apoC-III, and apoE in these mice. In normolipidemic women, apoA-II concentration was directly correlated with plasma triglyceride and inversely correlated with the HDL-apoC-II+apoE/apoC-III ratio [corrected]. HDL-mediated induction of LPL activity was inversely correlated with apoA-II and directly correlated with the HDL-apoC-II+apoE/apoC-III ratio [corrected]. Purified hapoA-II displaced apoC-II, apoC-III, and apoE from human HDL2. Human HDL3 was, compared to HDL2, enriched in apoA-II but poorer in apoC-II, apoC-III, and apoE.


CONCLUSIONS
ApoA-II plays a crucial role in triglyceride catabolism by regulating LPL activity, at least in part, through HDL proteome modulation.
Julve
Josep
J
Hospital de la Santa Creu i Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Escolà-Gil
Joan Carles
JC
Rotllan
Noemi
N
Fiévet
Catherine
C
Vallez
Emmanuelle
E
de la Torre
Carolina
C
Ribas
Vicent
V
Sloan
John H
JH
Blanco-Vaca
Francisco
F
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood* / Q000235:genetics; D053304:Apolipoprotein C-II / Q000097:blood; D053305:Apolipoprotein C-III / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004041:Dietary Fats / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007422:Intestines / Q000201:enzymology; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000097:blood*; D053439:Lipoproteins, HDL2 / Q000097:blood*; D053440:Lipoproteins, HDL3 / Q000097:blood*; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009391:Nephelometry and Turbidimetry; D019518:Postprandial Period; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*; D015854:Up-Regulation
C115794:APOA2 protein, human; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001057:Apolipoproteins E; D015415:Biomarkers; D004041:Dietary Fats; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D020543:Proteome; D014280:Triglycerides; D008071:Lipoprotein Lipase