Metabolism of apolipoprotein A-II containing triglyceride rich ApoB lipoproteins in humans
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CitationDesai, Nirav K., Esther M. Ooi, Paul D. Mitchell, Jeremy Furtado, and Frank M. Sacks. 2015. “Metabolism of Apolipoprotein A-II Containing Triglyceride Rich ApoB Lipoproteins in Humans.” Atherosclerosis 241 (2) (August): 326–333. doi:10.1016/j.atherosclerosis.2015.05.013.
To characterize human triglyceride-rich lipoproteins (TRL) with and without apoA-II and to study their metabolism in vivo.
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.
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.
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.
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