VLDL-TG kinetics: a dual isotope study for quantifying VLDL-TG pool size, production rates, and fractional oxidation in humans

Abstract

Very-low-density lipoproteins (VLDLs) are large, complex particles containing both surface proteins (e.g., ApoB100) and core lipids, e.g., cholesterol and triglycerides (TG). Whereas ApoB100 kinetics have been thoroughly studied, accurate measurement of VLDL-TG kinetics have proven difficult due to either complex mathematics or laborious procedures. The present study was therefore designed to measure VLDL-TG kinetics by dual isotope ex vivo labeled VLDL-TG tracers and well-established kinetics equations (bolus injection or the primed continuous infusion). Ten healthy Caucasian men [age, 23 ± 3 yr old (mean ± SD); body mass index, 24.7 ± 1.3 kg/m2] were included in the study. VLDL-TG rate of appearance (Ra) was measured using a dual-tracer technique ([9,10-3H]-labeled VLDL-TG and [1-14C]-labeled VLDL-TG) to allow comparison of various bolus decay curve fits with the Ra obtained by the primed continuous infusion (PCI; considered the gold standard). In addition, VLDL-TG fatty acid oxidation was measured as14CO2in exhaled breath, using the hyamine trapping technique. Following a bolus injection, tracer decay was better described by a biexponential than a monoexponential fit ( r2= 0.99 ± 0.01 vs. 0.97 ± 0.04, respectively, P = 0.01). VLDL-TG Ra calculated using the PCI correlated significantly with the biexponential fit (ρ = 0.62, P < 0.05), whereas this was not the case for the monoexponential fit (ρ = −0.18, P = not significant). VLDL-TG Ra using the best fit of the bolus injection method (biexponential) was less than values obtained by the constant infusion technique [biexponential, 34.3 (range, 27.1–69.6) vs. PCI, 44.4 (range, 33.0–72.7), P < 0.05]. Fractional oxidation of VLDL-TG was 37.2 ± 8.8% at 240 min corresponding to 198.8 ± 55.9 kcal/day or 10.6 ± 3.3% of resting energy expenditure (REE). Our data demonstrate that VLDL-TG Ra measured by a biexponential fit to a bolus decay curve correlates well with VLDL-TG Ra measured by a primed continuous infusion, and therefore that a “second” peripheral VLDL-TG compartment with rapid exchange of TG exists. VLDL-TG volume of distribution is therefore greater than previously anticipated. Finally our data supports that VLDL-TG contributes quantitatively to REE.