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Atherosclerosis. 2015 Aug;241(2):326-33. doi: 10.1016/j.atherosclerosis.2015.05.013. Epub 2015 May 19.

Metabolism of apolipoprotein A-II containing triglyceride rich ApoB lipoproteins in humans.

Author information

1
Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
2
School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
3
Clinical Research Center, Boston Children's Hospital, Boston, MA, USA.
4
Department of Nutrition, Harvard School of Public Health and Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
5
Department of Nutrition, Harvard School of Public Health and Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: fsacks@hsph.harvard.edu.

Abstract

OBJECTIVE:

To characterize human triglyceride-rich lipoproteins (TRL) with and without apoA-II and to study their metabolism in vivo.

METHODS:

Plasma from 11 participants on a controlled diet given a bolus infusion of [D5]l-phenylalanine to label apoB was combined into four pools and applied to anti-apoA-II immunoaffinity columns. Fractions with and without apoA-II were separated into VLDL and IDL by ultracentrifugation; lipids and apolipoproteins were measured. For kinetic measurements, apoB was isolated and hydrolyzed to the constituent amino acids. Tracer enrichment was measured by GCMS. Metabolic rates were determined by SAAM-II.

RESULTS:

VLDL and IDL with apoA-II comprised 7% and 9% of total VLDL and IDL apoB respectively. VLDL with apoA-II was enriched in apoC-III, apoE, and cholesterol compared to VLDL without apoA-II. Mean apoB FCR of VLDL with apoA-II was significantly lower than for VLDL without apoA-II (2.80 ± 0.96 pools/day v.s. 5.09 ± 1.69 pools/day, P = 0.009). A higher percentage of VLDL with apoA-II was converted to IDL than was cleared from circulation, compared to VLDL without apoA-II (96 ± 8% vs. 45 ± 22%; P = 0.007). The rate constants for conversion of VLDL to IDL were similar for VLDL with and without apoA-II. Thus, a very low rate constant for clearance accounted for the lower FCR of VLDL with apoA-II.

CONCLUSION:

VLDL with apoA-II represents a small pool of VLDL particles that has a slow FCR and is predominantly converted to IDL rather than cleared from the circulation.

KEYWORDS:

Apolipoprotein A-II; Lipid metabolism; Triglyceride rich lipoproteins; VLDL

[Indexed for MEDLINE]
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