Models to interpret kinetic data in stable isotope tracer studies

Cobelli, Claudio; Toffolo, Gianna; Bier, Dennis M.; Nosadini, R.

doi:10.1152/ajpendo.1987.253.5.e551

Cited by 92 publications

(91 citation statements)

References 11 publications

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“…18 Kinetic analysis of tracer -tracee ratios were made with the simulation analysis modelling SAAM II program 19 (SAAM Institute Inc., Seattle, WA, USA). ApoA-I and B-100 data were analysed using a monoexponential function, assuming that the kinetics of these apolipoproteins are described by one single compartment.…”

Section: Modellingmentioning

confidence: 99%

High-density lipoprotein apolipoprotein A-I kinetics in obese insulin resistant patients. An in vivo stable isotope study

et al. 2002

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AIMS=HYPOTHESIS:Mechanisms responsible for the decreased high-density lipoprotein (HDL) cholesterol level associated with insulin resistance in obese patients are not clearly understood. To determine the influence of insulin resistance at an early stage on HDL metabolism, we performed a stable isotope kinetic study of apolipoprotein (apo) A-I, in five obese insulin resistant women with normal fasting triglycerides and without impaired glucose tolerance, and in five age-matched control women. METHODS: Each subject received a 16 h constant infusion of L-[1-13 C]leucine at 0.7 mg=kg=h following a primed bolus of 0.7 mg=kg. RESULTS: ApoA-I fractional catabolic rate (FCR) was significantly increased in insulin-resistant women compared to controls (0.316 AE 0.056 vs 0.210 AE 0.040 per day, P < 0.01), indicating a significant 50% increase of apoA-I catabolism, leading to an important reduction of plasma apoA-I residence time (3.25 AE 0.59 vs 4.92 AE 1.11, P < 0.01). ApoA-I production rate tended to be higher in insulin resistant women than in controls (364 AE 77 vs 258 AE 60 mg=l=day, P ¼ 0.13), but the difference was not statistically significant. ApoA-I FCR was correlated with triglycerides during the fed state (r ¼ 0.69; P ¼ 0.026) and HDL triglycerides -esterified cholesterol ratio (r ¼ 0.73; P ¼ 0.016), suggesting that alteration of apoA-I metabolism in insulin resistance may be partly related to HDL enrichment in triglycerides. CONCLUSIONS: Our kinetic study shows that patients, at an early stage of insulin resistance (without impaired glucose tolerance nor fasting hypertriglyceridaemia), already have a significant alteration of apoA-I metabolism (increased apoA-I catabolism), which is consistent with the increased risk of atherosclerosis in this population.

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Section: Modellingmentioning

confidence: 99%

High-density lipoprotein apolipoprotein A-I kinetics in obese insulin resistant patients. An in vivo stable isotope study

et al. 2002

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“…Isotope enrichment (%) and tracer/tracee ratio (%) were calculated from the observed ion current ratios by the method of Cobelli et al 24 Data in this format are analogous to specific radioactivity in radiotracer experiments. The isotopic enrichment of leucine in the apolipoproteins was expressed as tracer/tracee ratio (%).…”

Section: Isotopic Enrichment Determinationsmentioning

confidence: 99%

Human Apolipoprotein (Apo) B-48 and ApoB-100 Kinetics With Stable Isotopes

Welty

Lichtenstein

Barrett

et al. 1999

ATVB

101

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Abstract-The kinetics of apolipoprotein (apo) B-100 and apoB-48 within triglyceride-rich lipoproteins (TRLs) and of apoB-100 within IDL and LDL were examined with a primed-constant infusion of (5,5,5-2 H 3 ) leucine in the fed state (hourly feeding) in 19 subjects after consumption of an average American diet (36% fat). Lipoproteins were isolated by ultracentrifugation and apolipoproteins by SDS gels, and isotope enrichment was assessed by gas chromatography/mass spectrometry. Kinetic parameters were calculated by multicompartmental modeling of the data with SAAM II. The pool sizes (PS) of TRL apoB-48, VLDL apoB-100, and LDL apoB-100 were 17Ϯ10, 273Ϯ167, and 3325Ϯ1146 mg, respectively. There was a trend toward a faster fractional catabolic rate (FCR) for VLDL apoB-100 than for TRL apoB-48 (6.73Ϯ3.48 versus 5.02Ϯ2.07 pools/d, respectively, Pϭ0.06). The mean FCRs for IDL and LDL apoB-100 were 10.07Ϯ7.28 and 0.27Ϯ0.08 pools/d, respectively. The mean production rate (PR) of TRL apoB-48 was 6.5% of VLDL apoB-100 (1.3Ϯ0.90 versus 20.06Ϯ6.53 mg ⅐ kg. TRL apoB-48 PS was correlated with apoB-48 PR (rϭ0.780, PϽ0.0001) but not FCR (rϭϪ0.1810, Pϭ0.458). VLDL apoB-100 PS was correlated with both PR (rϭ0.713, Pϭ0.0006) and FCR (rϭϪ0.692, Pϭ0.001) of VLDL apoB-100 and by apoB-48 PR (rϭ0.728, Pϭ0.0004). LDL apoB-100 PS was correlated with FCR (rϭϪ0.549, Pϭ0.015). These data indicate that (1) the FCRs of TRL apoB-48 and VLDL apoB-100 are similar in the fed state, (2) TRL apoB-48 PS is correlated with TRL apoB-48 PR, (3) VLDL apoB-100 PS is correlated with both PR and FCR of VLDL apoB-100 and PR of TRL apoB-48, and (4) LDL apoB-100 PS is correlated with LDL FCR. Key Words: apolipoprotein B Ⅲ metabolism Ⅲ stable isotopes Ⅲ LDL cholesterol Ⅲ lipoproteins T he mechanisms regulating the synthesis and secretion of apolipoprotein (apo) B-100 and apoB-48 are incompletely understood but are of importance because elevated levels of apoB, the main protein in LDL, are associated with an increased risk of coronary heart disease. 1 ApoB exists in 2 forms in plasma, apoB-100 and apoB-48, 2 both of which are products of the same structural gene on chromosome 2. 3 ApoB-100 is synthesized by the liver and secreted within VLDLs, which are metabolized in plasma to form LDL. ApoB-100 contains the LDL receptor-binding domain; therefore, VLDL remnants (IDL) and LDL are removed from the circulation by binding to hepatic LDL receptors. 2 Synthesized in the intestine in response to dietary fat, apoB-48 is produced as a result of a premature stop codon at the apoB-100 codon 2153 by tissue-specific mRNA processing and secreted within chylomicrons. 4 Both chylomicrons and VLDL are the major triglyceride carriers in plasma, and the triglycerides therein are hydrolyzed by lipoprotein lipase to form chylomicron remnants and VLDL remnants, respectively. ApoB-48 does not contain an LDL receptor-binding domain; therefore, the chylomicron remnants are most likely taken up by the liver by receptors that recognize apo E. 5,6 Increasing evidence suggests that chylomi...

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“…Mole percent excess (MPE) was calculated from enrichment calibration curves that were derivatised and run with the study samples. This method of calculation is equivalent to the method of Cobelli et al, 1987. Calculation of apoB100 production Fractional synthetic rate (FSR) of VLDL apoB100 (as poolsah) was calculated from the rate of incorporation of 13 C-leucine into the circulating protein and application of monocompartmental kinetics and a monocompartmental model (Parhofer et al, 1991) A t Ap 1 À e Àk tÀd where A(t) is the traceratracee (labelledaunlabelled leucine) ratio at time t, Ap is the precursor traceratracee ratio (taken as the plasma aKIC enrichment), d is the delay time until the appearance of labelled apoB100 in the VLDL fraction and k represents the FSR of VLDL apoB100. The absolute production rate (APR) of VLDL apoB100 was calculated as: APR FSR (poolsah) 6 apolipoprotein pool size (mg)…”

Section: Measurement Of Stable Isotope Enrichmentmentioning

confidence: 99%

Effects of fish oil supplementation on apolipoprotein B100 production and lipoprotein metabolism in normolipidaemic males

et al. 1998

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Objective: To evaluate the effects of four weeks of ®sh oil supplementation on apolipoprotein B100 production and lipoprotein metabolism in normolipidaemic males. Design and subjects: Very low density lipoprotein (VLDL) apolipoprotein B100 (apoB100) kinetics in ten healthy, white males, aged 22±43 y (mean 32 y) were investigated using a 13 C-leucine technique and gas chromatography-mass spectrometry before and after ®sh oil supplementation. Intervention: All subjects received 10 g (1.8 g EPA, 1.2 g DHA)ad of ®sh oil concentrate for four weeks. Results: Fish oil supplementation resulted in a decrease of total plasma VLDL (mean AE s.d. 1.11 AE 0.41 vs 0.87 AE 0.28 mmolal, P`0.05) and triacylglycerol concentrations (0.74 AE 0.27 vs 0.48 AE 0.21 mmolal, P`0.01). VLDL apoB100 pool size was decreased without alteration of the fractional synthetic rate but a signi®cant decrease of apoB100 production (2.23 AE 0.90 vs 1.54 AE 0.52 mgadlah, P`0.02). Following ®sh oil supplementation plasma concentrations of glucose and insulin as well as lipoprotein and hepatic lipase activities were unchanged. Fasting plasma concentrations of non-esteri®ed fatty acid (NEFA) were decreased (0.45 AE 0.12 vs 0.33 AE 0.10 mmolal, P`0.05). Conclusions: Dietary supplementation with ®sh oil in healthy males results in decreased VLDL-triacylglycerol concentrations through a decrease in VLDL particle synthesis. The decrease in NEFA substrate supply also contributes. Sponsorship: Fish oil (Maxepa 1 ) was supplied by Seven Seas Ltd, Hull, England, free of charge. Dr OAF Bodamer was funded by the`Deutsche Forschungsgemeinschaft' (Bo 1193a1-2).

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Models to interpret kinetic data in stable isotope tracer studies

Cited by 92 publications

References 11 publications

High-density lipoprotein apolipoprotein A-I kinetics in obese insulin resistant patients. An in vivo stable isotope study

High-density lipoprotein apolipoprotein A-I kinetics in obese insulin resistant patients. An in vivo stable isotope study

Human Apolipoprotein (Apo) B-48 and ApoB-100 Kinetics With Stable Isotopes

Effects of fish oil supplementation on apolipoprotein B100 production and lipoprotein metabolism in normolipidaemic males

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