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Am J Physiol Endocrinol Metab (September 22, 2009). doi:10.1152/ajpendo.00366.2009
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RESEARCH ARTICLE

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

Lars Sorensen,1 Lars Gormsen, MD PhD,2,* and Søren Nielsen3

1Dept. M (endocrinology and diabetes), Aarhus University Hospital 2Department of Nuclear Medicine, Aarhus University Hospital, Aarhus, Denmark 3Insitute of Anatomy, University of Aarhus

Submitted 4 June 2009 ; revised 2 September 2009 ; accepted in final form 21 September 2009

Very-low-density-lipoproteins (VLDLs) are large, complex particles containing surface proteins (e.g. ApoB100) and core lipids (e.g. cholesterol and triglycerides). Whereas ApoB100 kinetics has been thoroughly studied, accurate measurement of VLDL-TG kinetics has 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 years (mean±SD), BMI 24.7±1.3kg/m2) were included in the study. VLDL-TG rate of appearance (Ra) was measured using a dual tracer technique ([9,10-3H]VLDL-TG and [1-14C]VLDL-TG) to allow comparison of various bolus decay curve fits with the Ra obtained by the primed-continuous infusion (considered the Gold Standard). In addition, VLDL-TG fatty acid oxidation was measured as 14CO2 in exhaled breath using the hyamine trapping technique. Following a bolus injection, tracer decay was better described by a bi-exponential than a mono-exponential fit (BIEXP: r2=0.99±0.01 vs. MONOEXP: 0.97±0.04, p=0.01). VLDL-TG Ra calculated using the primed-continuous infusion (PCI) correlated significantly with the bi-exponential fit (rho=0.62, p<0.05) whereas this was not the case for the mono-exponential fit (rho=-0.18, p=NS). VLDL-TG Ra using the best fit of the bolus injection method (BIEXP) was less than values obtained by the constant infusion technique (BIEXP: 34.3 (27.1-69.6) vs. PCI: 44.4 (33.0-72.7), p<0.05). Fractional oxidation of VLDL-TG was 37.2±8.8% at 240 min corresponding to 198.8±55.9kcal/day or 10.6±3.3% of resting energy expenditure (REE). Our data demonstrate: 1) that VLDL-TG Ra measured by a biexponential fit to a bolus decay curve correlates well with VLDL-TG Ra measured by a primed-continous infusion, and therefore 2) 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 3) VLDL-TG contributes quantitatively to REE.

VLDL-triglycerides; lipoproteins; tracer kinetics; methods



* Department of Nuclear Medicine, Aarhus University Hospital, Aarhus, Denmark lars.christian.gormsen{at}ki.au.dk







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