Direct association between the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 and plasma mevalonic acid and lathosterol concentrations in man.
Apolipoprotein B-100 (apo B) is the principal structural and functional protein of the pro-atherogenic lipoproteins, but its homeostasis in man has not been clearly established. The hepatic availability of cholesterol substrate may be a determining factor. We examined whether there was a direct correlation between plasma concentrations of mevalonic acid (MVA) and lathosterol (indices of in vivo cholesterol synthesis) and hepatic secretion of very-low-density lipoprotein (VLDL) apo B in 13 normolipidaemic, healthy male subjects. The secretion of VLDL apo B was measured using a primed constant intravenous infusion of 1-[13C]-leucine (1 mg/kg per h) over 8 h. Gas-chromatography mass spectrometry (GCMS) was used to derive isotopic enrichment of apo B and fractional turnover rate was calculated using a monoexponential function. There was a highly significant positive correlation between the absolute secretion rate (ASR) of VLDL apo B and the plasma concentrations of mevalonic acid (r = 0.72, P = 0.005) and lathosterol (r = 0.81, P = 0.001) and the lathosterol:cholesterol ratio (r = 0.79, P = 0.001). In multiple regression analysis, these correlations remained significant after adjusting for waist circumference, age, apolipoprotein E genotype and dietary fat intake. The data further support the notion that the availability of cholesterol substrate regulates the hepatic secretion rate of apo B.
Riches
F M
FM
University Department of Medicine, University of Western Australia, Royal Perth Hospital.
Watts
G F
GF
Naoumova
R P
RP
Kelly
J M
JM
Croft
K D
KD
Thompson
G R
GR
D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism*; D002247:Carbon Isotopes; D002784:Cholesterol / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D016014:Linear Models; 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; D002247:Carbon Isotopes; D008079:Lipoproteins, VLDL; C001521:lathosterol; D002784:Cholesterol; D008798:Mevalonic Acid