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 functiona l protein of the pro-atherogenic lipoproteins, but its homeostasis in man has not been clearly established. The hepatic availability of chol esterol substrate may be a determining factor. We examined whether the re 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 I-[C-13 ]-leucine (1 mg/kg per h) over 8 h. Gas-chromatography mass spectromet ry (GCMS) was used to derive isotopic enrichment of apo B and fraction al turnover rate was calculated using a monoexponential function. Ther e was a highly significant positive correlation between the absolute s ecretion rate (ASR) of VLDL apo B and the plasma concentrations of mev alonic 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 mult iple regression analysis, these correlations remained significant afte r adjusting for waist circumference, age, apolipoprotein E genotype an d dietary fat intake. The data further support the notion that the ava ilability of cholesterol substrate regulates the hepatic secretion rat e of apo B. (C) 1997 Elsevier Science Ireland Ltd.