AJP - Endocrinology and Metabolism, Vol 273, Issue 3 E462-E470, Copyright © 1997 by American Physiological Society

ARTICLES

Inhibition of cholesterogenesis decreases hepatic secretion of apoB-100 in normolipidemic subjects

G. F. Watts, R. P. Naoumova, J. M. Kelly, F. M. Riches, K. D. Croft and G. R. Thompson
Department of Medicine, University of Western Australia, Royal Perth Hospital, Perth, Australia.

We examined the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the kinetics of very low-density lipoprotein apolipoprotein B-100 (VLDL apoB) in 13 normolipidemic men in a placebo-controlled crossover study. Simvastatin significantly decreased the plasma concentrations of low-density lipoprotein (LDL) cholesterol by 36%, triglycerides by 26%, mevalonic acid by 34%, and lathosterol by 32%. Hepatic secretion of VLDL apoB was measured using a primed constant intravenous infusion of [1-13C]leucine with monitoring of isotopic enrichment of apoB by gas chromatography-mass spectrometry; fractional turnover rate was derived using a monoexponential function. Simvastatin decreased VLDL apoB pool size by 53% and the hepatic secretion rate of VLDL apoB by 46% but did not significantly alter its fractional catabolism. The change in hepatic VLDL apoB secretion was significantly and independently correlated with changes in plasma mevalonic acid and lathosterol concentrations and the lathosterol-to-cholesterol ratio. The data support the hypothesis that the rate of de novo cholesterol synthesis directly regulates the hepatic secretion of VLDL apoB in normal subjects.

This article has been cited by other articles:

				R. Ramakrishnan Studying apolipoprotein turnover with stable isotope tracers: correct analysis is by modeling enrichments J. Lipid Res., December 1, 2006; 47(12): 2738 - 2753. [Abstract] [Full Text] [PDF]

				S. Pal, N. Ho, C. Santos, P. Dubois, J. Mamo, K. Croft, and E. Allister Red Wine Polyphenolics Increase LDL Receptor Expression and Activity and Suppress the Secretion of ApoB100 from Human HepG2 Cells J. Nutr., March 1, 2003; 133(3): 700 - 706. [Abstract] [Full Text] [PDF]

				A. D. Sniderman, T. Scantlebury, and K. Cianflone Hypertriglyceridemic HyperapoB: The Unappreciated Atherogenic Dyslipoproteinemia in Type 2 Diabetes Mellitus Ann Intern Med, September 18, 2001; 135(6): 447 - 459. [Abstract] [Full Text] [PDF]

				F. Diraison, V. Large, C. Maugeais, M. Krempf, and M. Beylot Noninvasive tracing of human liver metabolism: comparison of phenylacetate and apoB-100 to sample glutamine Am J Physiol Endocrinol Metab, September 1, 1999; 277(3): E529 - E536. [Abstract] [Full Text] [PDF]

				L. J. Wilcox, P. H. R. Barrett, and M. W. Huff Differential regulation of apolipoprotein B secretion from HepG2 cells by two HMG-CoA reductase inhibitors, atorvastatin and simvastatin J. Lipid Res., June 1, 1999; 40(6): 1078 - 1089. [Abstract] [Full Text]

				Z. Zhang, K. Cianflone, and A. D. Sniderman Role of Cholesterol Ester Mass in Regulation of Secretion of ApoB100 Lipoprotein Particles by Hamster Hepatocytes and Effects of Statins on That Relationship Arterioscler. Thromb. Vasc. Biol., March 1, 1999; 19(3): 743 - 752. [Abstract] [Full Text] [PDF]

				H. Jiang, H. N. Ginsberg, and X. Wu Glucose does not stimulate apoprotein B secretion from HepG2 cells because of insufficient stimulation of triglyceride synthesis J. Lipid Res., November 1, 1998; 39(11): 2277 - 2285. [Abstract] [Full Text]