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

- We studied the kinetics of VLDL with and without apoA-II in humans.
- A small percentage of VLDL and IDL contains apoA-II.
- VLDL with apoA-II has a slower FCR than VLDL without apoA-II.
- VLDL with apoA-II has greatly reduced clearance from plasma compared to VLDL without apoA-II.
- VLDL with apoA-II has similar rate of conversion to IDL as VLDL without apoA-II.

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