Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production.
OBJECTIVE
We addressed the role of the low-density lipoprotein (LDL) receptor in determining clearance rates and production rate (PR) of apolipoprotein B (apoB) in humans.


RESULTS
Kinetic studies using endogenous labeling of apoB with deuterated leucine were performed in 7 genetically defined patients with homozygous familial hypercholesterolemia (FH) and compared with 4 controls. The fractional catabolic rates (FCR) and PRs for apoB were determined by multicompartmental modeling. The FCRs of very-low-density lipoprotein 1 (VLDL1), VLDL2, intermediate-density lipoprotein (IDL), and LDL apoB were lower in FH than in controls, with the LDL apoB FCR being significantly lower (0.148+/-0.049 versus 0.499+/-0.099 pools x d(-1); P=0.008). Whereas receptor-defective FH patients had a total apoB PR similar to controls, receptor-null FH patients had a significantly greater total apoB PR than controls (35.97+/-10.51 versus 21.32+/-4.21 mg x kg(-1) x d(-1), respectively; P=0.02).


CONCLUSIONS
This first study of apoB metabolism in homozygous FH using endogenous labeling with stable isotopes demonstrates that the LDL receptor contributes significantly to the clearance of LDL from plasma but plays a lesser role in the clearance of larger apoB-containing lipoproteins. Furthermore, these data also indicate that absence of a LDL receptor in humans substantially influences the apoB PR in vivo.
Millar
John S
JS
Department of Medicine, University of Pennsylvania, 644 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104, USA. jsmillar@mail.med.upenn.edu
Maugeais
Cyrille
C
Ikewaki
Katsunori
K
Kolansky
Daniel M
DM
Barrett
P Hugh R
PH
Budreck
Elaine C
EC
Boston
Raymond C
RC
Tada
Norio
N
Mochizuki
Seibu
S
Defesche
Joep C
JC
Wilson
James M
JM
Rader
Daniel J
DJ
D000293:Adolescent; D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D005260:Female; D006720:Homozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism*; D007930:Leucine / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D014316:Tritium
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D011973:Receptors, LDL; D014316:Tritium; D007930:Leucine