Human apolipoprotein A-IV metabolism within triglyceride-rich lipoproteinsand plasma

In order to investigate the metabolism of apo A-IV within TRL and plasma, w e assessed TRL and plasma apo A-IV kinetics in 19 and 4 subjects, respectiv ely, consuming an average US diet for a 6-week period. At the end of this d iet study, each subject received a primed-constant infusion of deuterated l eucine over a 15 h time period with hourly feeding, and blood samples were drawn at IO time points. TRL was separated by ultracentrifugation. Apo A-IV was isolated by immunoprecipitation and/or SDS-PAGE. Apo A-IV concentratio ns were determined by immunoelectrophoresis. Stable isotope tracer/tracee r atios were measured by gas chromatography/mass spectrometry, and the data w ere analyzed by multicompartmental modeling. The mean concentrations of pla sma and TRL apo A-IV during the isotope infusion period were 21.0 +/- 3.2 a nd 0.66 +/- 0.25 mg/dl, respectively, and these values were 11.5 and 30.5% higher than those of fasting samples. The mean TRL and plasma apo A-IV resi dence times (RT) were 1.97 +/- 0.57 and 2.71 +/- 0.65 days, and transport r ates (TR) were 0.17 +/- 0.19 and 3.90 +/- 1.24 mg/kg per day, respectively. There were significant correlations between TRL apo A-IV concentrations an d TR (r(2) = 0.79, P < 0.001), and between TRL apo A-IV pool size and TRL c holesterol levels (r(2) = 0.29, P = 0.02). Our data indicated that; (1) TRL apo A-IV has a RT of 1.97 days which is similar to that earlier reported f or HDL apo A-IV; (2) Apo A-IV recirculates between TRL and other slowly tur ning over pools; (3) the primary determinant of TRL apo A-TV levels is its TR; and (4) there is no correlation between TRL apo A-IV and apo B48 fracti onal catabolism in TRL. (C) 2001 Elsevier Science Ireland Ltd. All rights r eserved.