Nascent very-low-density lipoprotein triacylglycerol hydrolysis by lipoprotein lipase is inhibited by apolipoprotein E in a dose-dependent manner.
In the present study it was investigated whether apolipoprotein (apoE) can inhibit the lipoprotein lipase (LPL)-mediated hydrolysis of very-low-density-lipoprotein (VLDL) triacylglycerols (TAGs). Previous studies have suggested such an inhibitory role for apoE by using as a substrate for LPL either plasma VLDL or artificial TAG emulsions. To mimic the in vivo situation more fully, we decided to investigate the effect of apoE on the LPL-mediated TAG hydrolysis by using VLDL from apoE-deficient mice that had been enriched with increasing amounts of apoE. Furthermore, since plasma VLDL isolated from apoE-deficient mice was relatively poor in TAGs and strongly enriched in cholesterol as compared with VLDL from wild-type mice, we used nascent VLDL obtained by liver perfusions. Nascent VLDL (d<1. 006) isolated from the perfusate of the apoE-deficient mouse liver was rich in TAGs. Addition of increasing amounts of apoE to apoE-deficient nascent VLDL effectively decreased TAG lipolysis as compared with that of apoE-deficient nascent VLDL without the addition of apoE (63.1+/-6.3 and 20.8+/-1.8% of the control value at 2.7 microg and 29.6 microg of apoE/mg of TAG added respectively). Since, in vivo, LPL is attached to heparan sulphate proteoglycans (HSPG) at the endothelial matrix, we also performed lipolysis assays with LPL bound to HSPG in order to preserve the interaction of the lipoprotein particle with the HSPG-LPL complex. In this lipolysis system a concentration-dependent decrease in the TAG lipolysis was also observed with increasing amounts of apoE on nascent VLDL, although to a lesser extent than with LPL in solution (72.3+/-3.6% and 56.6+/-1.7% of control value at 2.7 microg and 29.6 microg of apoE/mg TAGs added respectively). In conclusion, the enrichment of the VLDL particle with apoE decreases its suitability as a substrate for LPL in a dose-dependent manner.
Jong
M C
MC
TNO-Prevention and Health, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands.
Dahlmans
V E
VE
Hofker
M H
MH
Havekes
L M
LM
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D014280:Triglycerides / Q000378:metabolism*
D001057:Apolipoproteins E; D019812:Heparan Sulfate Proteoglycans; D008055:Lipids; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase