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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M500528-JLR200 on May 9, 2006

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Journal of Lipid Research, Vol. 47, 1771-1779, August 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Metabolism of apoB lipoproteins of intestinal and hepatic origin during constant feeding of small amounts of fat

Chunyu Zheng*, Katsunori Ikewaki{dagger}, Brian W. Walsh§ and Frank M. Sacks1,*

* Department of Nutrition, Harvard School of Public Health, Boston, MA 02115
{dagger} Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan 105-8461
§ Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115

Published, JLR Papers in Press, May 9, 2006.

1 To whom correspondence should be addressed. e-mail: fsacks{at}hsph.harvard.edu

We aimed to identify mechanisms by which apolipoprotein B-48 (apoB-48) could have an atherogenic role by simultaneously studying the metabolism of postprandial apoB-48 and apoB-100 lipoproteins. The kinetics of apoB-48 and apoB-100, each in four density subfractions of VLDL and intermediate density lipoprotein (IDL), were studied by stable isotope labeling in a constantly fed state with half-hourly administration of almond oil in five postmenopausal women. A non-steady-state, multicompartmental model was used. Despite a much lower production rate, VLDL and IDL apoB-48 shared a similar secretion pattern with apoB-100: both were directly secreted into all fractions with similar percentage mass distributions. Fractional catabolic rates (FCRs) of apoB-48 and apoB-100 were similar in VLDL and IDL. We identified a fast turnover compartment of light VLDL that had a residence time of <30 min for apoB-48 and apoB-100. Finally, a high secretion rate of apoB-48 was associated with a slow FCR of VLDL and IDL apoB-100. In conclusion, the intestine secretes a spectrum of apoB lipoproteins, similar to what the liver secretes, albeit with a much lower secretion rate. Once in plasma, intestinal and hepatic triglyceride-rich lipoproteins have similar rates of clearance and participate interactively in similar metabolic pathways, with high apoB-48 production inhibiting the clearance of apoB-100.

Supplementary key words kinetics • stable isotopes • triglyceride-rich lipoproteins • apolipoprotein B-48 • apolipoprotein B-100


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