Direct correlation between cholesterol synthesis and hepatic secretion of apolipoprotein B-100 in normolipidemic subjects.
The regulation of apolipoprotein B-100 (apo B) metabolism in man is not fully understood. In vitro studies suggest a key role for the hepatic availability of cholesterol substrate. We therefore examined whether there was a direct association between plasma mevalonic acid (MVA) concentration (an index of in vivo cholesterol synthesis) and hepatic secretion of very-low-density lipoprotein (VLDL) apo B in eight normolipidemic, healthy adult subjects. Hepatic secretion of VLDL apo B was estimated by endogenous labeling of apo B with an 8-hour primed, constant infusion of 1-13C-leucine. Isotopic enrichment of VLDL apo B was measured by gas chromatography-mass spectrometry (GCMS), from which the fractional secretion rate (FSR) was derived by a modified monoexponential function. Plasma concentration of MVA was measured by gas chromatography-electron-capture mass spectrometry in blood samples taken at 9 AM. The absolute secretion rate (ASR) of VLDL apo B (mean +/- SD) was 9.7 +/- 2.6 mg/kg/d, and MVA concentration was 5.0 +/- 2.5 ng/mL. There was a highly significant positive correlation between ASR of VLDL apoB and plasma MVA (r = .88, P = .004), which persisted after adjusting for apo E phenotype. The findings suggest that in vivo cholesterol synthesis is a determinant of hepatic secretion of apo B in normolipidemic subjects.
Watts
G F
GF
Department of Medicine, University of Western Australia, Perth.
Naoumova
R
R
Cummings
M H
MH
Umpleby
A M
AM
Slavin
B M
BM
Sönksen
P H
PH
Thompson
G R
GR
D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007525:Isoelectric Focusing; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008798:Mevalonic Acid / Q000097:blood; D008875:Middle Aged
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D008798:Mevalonic Acid