DIRECT CORRELATION BETWEEN CHOLESTEROL-SYNTHESIS AND HEPATIC SECRETION OF APOLIPOPROTEIN B-100 IN NORMOLIPIDEMIC SUBJECTS

The regulation of apolipoprotein B-100 (ape B) metabolism in man is no t fully understood, In vitro studies suggest a key role for the hepati c availability of cholesterol substrate. We therefore examined whether there was a direct association between plasma mevalonic acid (MVA) co ncentration (an index of in vivo cholesterol synthesis) and hepatic se cretion of very-low-density lipoprotein (VLDL) apo B in eight normolip idemic, healthy adult subjects. Hepatic secretion of VLDL apo B was es timated by endogenous labeling of apo B with an 8-hour primed, constan t infusion of 1-C-13-leucine, Isotopic enrichment of VLDL apo B was me asured by gas chromatography-mass spectrometry (GCMS), from which the fractional secretion rate (FSR) was derived by a modified monoexponent ial function. Plasma concentration of MVA was measured by gas chromato graphy-electron-capture mass spectrometry in blood samples taken at 9 AM, The absolute secretion rate (ASR) of VLDL apo B (mean +/- so) was 9.7 +/- 2.6 mg/kg/d, and MVA concentration was 5.0 +/- 2.5 ng/mL. Ther e was a highly significant positive correlation between ASR of VLDL ap oB and plasma MVA (r = .88, P = .004), which persisted after adjusting for apo E phenotype. The findings suggest that in vivo cholesterol sy nthesis is a determinant of hepatic secretion of apo B in normolipidem ic subjects. Copyright (C) 1995 by W.B. Saunders Company