Lipolysis exposes unreactive endogenous apolipoprotein E-3 in human and rat plasma very low density lipoprotein.
Endogenous apolipoprotein E in VLDL is poorly expressed in receptor binding processes. Yet catabolism of VLDL-remnants by cellular receptors depends on functional apo E molecules. To better understand remnant catabolism phenomena, we determined the metabolism of VLDL and post-lipolysis VLDL by cultured cells. Partial lipolysis was achieved by incubation of VLDL with lipoprotein lipase in vitro (human) or recirculation (rat) in supradiaphragmatic animals. Lipolyzed VLDL exhibit metabolic activities 2-20-fold higher than control VLDL, that are saturable and dependent on the presence of LDL receptors. The ligand responsible for receptor interaction of lipolyzed VLDL (apo E or apo B-100) and its source (endogenous or transferred) was studied with monoclonal antibodies and with lipoproteins from E-3/3 and E-2/2 subjects. The data unequivocally proved that lipolysis causes exposure of unreactive endogenous apo E-3 at the VLDL surface, possibly by a change of conformation of the protein. Apo B-100 becomes biologically expressed only in lipolyzed VLDL-III. Lipolyzed VLDL, however, is less reactive to exogenous apo E-3 than control VLDL indicating that endogenous and exogenous apo E are oriented differently in VLDL. It is proposed that VLDL delivers triglycerides to tissues when apo E is unreactive but becomes a remnant after the protein becomes exposed and directs the particles from lipoprotein lipase sites to cellular receptors.
Sehayek
E
E
Department of Medicine B, Hadassah University Hospital, Jerusalem, Israel.
Lewin-Velvert
U
U
Chajek-Shaul
T
T
Eisenberg
S
S
D000818:Animals; D053299:Apolipoprotein B-100; D053318:Apolipoprotein E3; D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism*; D001692:Biological Transport; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008066:Lipolysis; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D053299:Apolipoprotein B-100; D053318:Apolipoprotein E3; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides