Abstract
Tracer methods for VLDL-TG kinetics vary in their ability to account for the effect of tracer recycling, which can influence the calculation of VLDL-TG fractional catabolic rates (FCRs). We evaluated a novel approach, involving stable isotopically labeled glycerol or palmitate tracers in conjunction with compartmental modeling, for measuring VLDL-TG kinetics in normolipidemic human subjects. When administered as a bolus simultaneously, both tracers provided identical VLDL-TG FCRs when the data were analyzed by a compartmental model that accounted for hepatic lipid tracer recycling, but not by non-compartmental analysis. The model-derived FCR was greater than that determined using a non-compartmental approach, and was 2- to 3-fold higher than that usually reported by using a bolus of radioactive [3H]glycerol. When palmitate tracer was given as a constant infusion, VLDL-TG turnover appeared 5-fold slower, because tracer recycling through hepatic lipid pools could not be resolved with the infusion protocol. We conclude that accounting for tracer recycling, particularly the contribution of hepatic glycerolipid pools, is essential to accurately measure VLDL-TG kinetics, and that bolus injection of stable isotopically labeled glycerol or palmitate tracers in conjunction with compartmental modeling analysis offers a reliable approach for measuring VLDL-TG kinetics.—Patterson, B. W., B. Mittendorfer, N. Elias, R. Satyanarayana, and S. Klein. Use of stable isotopically labeled tracers to measure very low density lipoprotein-triglyceride turnover.
Highlights
Tracer methods for VLDL-TG kinetics vary in their ability to account for the effect of tracer recycling, which can influence the calculation of VLDL-TG fractional catabolic rates (FCRs)
There was usually a 30-min delay before glycerol and palmitate tracer-tracee ratio (TTR) was detectable in VLDLTG, which peaked at 1–2 h after bolus tracer injection
The gas chromatography-mass spectrometry (GC-MS) and kinetic analyses of the glycerol tracer in VLDL-TG were based on measuring the TTR from the mϩ5/mϩ0 ratio of glycerol in VLDL-TG
Summary
Tracer methods for VLDL-TG kinetics vary in their ability to account for the effect of tracer recycling, which can influence the calculation of VLDL-TG fractional catabolic rates (FCRs). One common approach is to inject a bolus of tracer and determine the subsequent monoexponential slope of the decline in plasma VLDL-TG specific radioactivity [4,5,6,7] This approach can underestimate the true VLDLTG turnover rate because it does not account for tracer recycling. A constant infusion of stable isotopically labeled glycerol or palmitate has been used to measure VLDL-TG turnover rates by fitting the data to a monoexponential rise-to-plateau model (21 – 23). This method does not account for the con-
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