Differential metabolism of human VLDL according to content of ApoE and ApoC-III.
We studied the metabolism of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) particles that did or did not have apolipoprotein E (apoE) in 12 normolipidemic women by endogenously labeling plasma apolipoprotein B. The plasma was separated into bound (E+) and unbound (E-) fractions by use of a monoclonal antibody (1D7), and the fractions were ultracentrifuged to yield E+ and E- subfractions of light and dense VLDL and IDL. VLDL E+ and IDL E+ were produced mainly by the liver. VLDL E+ and IDL E+ had lower fractional catabolic rates and much higher apolipoprotein C-III (apoC-III) content than did the corresponding E- particles. Most light VLDL apoE+ underwent lipolysis to dense VLDL E+ with reduced apoC-III content, which was removed from the circulation without conversion to IDL. In contrast, most light VLDL apoE-, poor in apoC-III, was removed from the circulation, and a smaller proportion underwent lipolysis to dense VLDL E-. Most dense VLDL E- underwent lipolysis to IDL E-. The rate constant for lipolysis of dense VLDL to IDL was greater for E- than for E+, and the rate constant for clearance from plasma was greater for dense VLDL E+ than for E-. In conclusion, metabolism of human VLDL particles is influenced by their content of apoE, further modulated by the coexistence of apoC-III.
Tomiyasu
K
K
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
Walsh
B W
BW
Ikewaki
K
K
Judge
H
H
Sacks
F M
FM
D000368:Aged; D000483:Alleles; D000596:Amino Acids / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000378:metabolism; D001056:Apolipoproteins C / Q000032:analysis*; D001057:Apolipoproteins E / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL / Q000737:chemistry* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL