Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency.
The cholesteryl ester transfer protein (CETP) transfers lipids among lipoprotein particles and plays a central role in lipoprotein metabolism. Humans with genetic deficiency of CETP have both elevated HDL cholesterol and apolipoprotein A-I concentrations as well as decreased LDL cholesterol and apolipoprotein B levels. The present study was undertaken to elucidate the metabolic basis for the decreased LDL cholesterol and apo B levels in CETP deficiency. We conducted a series of in vivo apo B kinetic studies in tow unrelated homozygotes with CETP deficiency and in control subjects. A primed constant infusion of stable isotopically labeled phenylalanine was administered to the two CETP deficient subjects and control subjects and apo B kinetic parameters in VLDL, intermediate density lipoproteins, and LDL were obtained by using a multicompartmental model. The fractional catabolic rates (FCR) of LDL apo B were significantly increased in the CETP-deficient subjects (0.56 and 0.75/d) compared with the controls (mean FCR of 0.39/d). Furthermore, the production rates of apo B in VLDL and intermediate density lipoprotein were decreased by 55% and 81%, respectively, in CETP deficiency compared with the controls. In conclusion, CETP-deficient subjects were demonstrated to have substantially increased catabolic rates of LDL apo B as the primary metabolic basis for the low plasma levels of LDL apo B. This result indicates that the LDL receptor pathway may be up-regulated in CETP deficiency.
Ikewaki
K
K
Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nishiwaki
M
M
Sakamoto
T
T
Ishikawa
T
T
Fairwell
T
T
Zech
L A
LA
Nagano
M
M
Nakamura
H
H
Brewer
H B
HB
Rader
D J
DJ
D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006023:Glycoproteins; D006720:Homozygote; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008954:Models, Biological; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol