Hepatic lipase promotes a loss of apolipoprotein A-I from triglyceride-enriched human high density lipoproteins during incubation in vitro.
Studies have been performed to investigate a possible mechanism to account for the low concentrations of apolipoproteins A-I (apo A-I) in subjects with hypertriglyceridemia. Incubation of human plasma in vitro with canine hepatic lipase resulted in the hydrolysis of approximately half the triglyceride in the high density lipoproteins (HDLs), but little change in the concentrations of other HDL constituents. However, when the plasma was supplemented with cholesteryl ester transfer protein and very low density lipoproteins to enrich the HDL with triglyceride, hepatic lipase promoted not only a significant reduction in HDL triglyceride acquired by the lipid transfer process but also an enhanced transfer of cholesteryl esters out of the particles. These changes were accompanied by a marked loss of apo A-I from HDL, which was demonstrated independently by ultracentrifugation, size-exclusion chromatography, and gradient gel-immunoblot analysis. The apo A-I lost from HDL was recovered in the "lipoprotein-free" fraction of plasma. The results of these studies indicate that primary reductions in the concentration of HDL core lipids in vitro are accompanied by a secondary loss of apo A-I from HDL. While recognizing the need for caution in any extrapolation from observations made in vitro to what may occur in vivo, these studies are nevertheless consistent with a proposition that the low concentration of apo A-I in subjects with hypertriglyceridemia is secondary to the reduced concentration of HDL core lipids in such subjects.
Clay
M A
MA
Baker Medical Research Institute, Melbourne, Australia.
Newnham
H H
HH
Barter
P J
PJ
D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000378:metabolism*; D002845:Chromatography; D004285:Dogs; D006801:Humans; D006868:Hydrolysis; D015228:Hypertriglyceridemia / Q000378:metabolism; D015151:Immunoblotting; D008049:Lipase / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D012016:Reference Values; D014280:Triglycerides / Q000378:metabolism
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D014280:Triglycerides; D008049:Lipase