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A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data.

ABSTRACT: Given the association of disturbances in non-esterified fatty acid (NEFA) metabolism with the development of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, computational models of glucose-insulin dynamics have been extended to account for the interplay with NEFA. In this study, we use arteriovenous measurement across the subcutaneous adipose tissue during a mixed meal challenge test to evaluate the performance and underlying assumptions of three existing models of adipose tissue metabolism and construct a new, refined model of adipose tissue metabolism. Our model introduces new terms, explicitly accounting for the conversion of glucose to glyceraldehye-3-phosphate, the postprandial influx of glycerol into the adipose tissue, and several physiologically relevant delays in insulin signalling in order to better describe the measured adipose tissues fluxes. We then applied our refined model to human adipose tissue flux data collected before and after a diet intervention as part of the Yoyo study, to quantify the effects of caloric restriction on postprandial adipose tissue metabolism. Significant increases were observed in the model parameters describing the rate of uptake and release of both glycerol and NEFA. Additionally, decreases in the model's delay in insulin signalling parameters indicates there is an improvement in adipose tissue insulin sensitivity following caloric restriction.

SUBMITTER: O'Donovan SD

PROVIDER: S-EPMC6890259 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data.

O'Donovan Shauna D SD Lenz Michael M Vink Roel G RG Roumans Nadia J T NJT de Kok Theo M C M TMCM Mariman Edwin C M ECM Peeters Ralf L M RLM van Riel Natal A W NAW van Baak Marleen A MA Arts Ilja C W ICW

PLoS computational biology 20191003 10

Given the association of disturbances in non-esterified fatty acid (NEFA) metabolism with the development of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, computational models of glucose-insulin dynamics have been extended to account for the interplay with NEFA. In this study, we use arteriovenous measurement across the subcutaneous adipose tissue during a mixed meal challenge test to evaluate the performance and underlying assumptions of three existing models of adipose tissue metaboli ...[more]

PMID: 31581241

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Project description:BackgroundKnowledge of the physiologic requirement for iron, the core index for the formulation of a dietary reference intake (DRI), is of great importance for the health of a pregnant woman and her fetus, and can help a mother accurately plan her iron supplementation. However, direct measurements of the physiologic requirement for iron during pregnancy are still lacking.MethodEleven women of reproductive age from Hebei Province, China, who planned to become pregnant in the near future, were enrolled between January and March 2015 and included in the final analysis. Subjects participated in a 2-week metabolic trial in which they consumed 50 mg of the stable isotope 58Fe, and were then followed for ~ 2 years. The abundance of 58Fe and the total iron concentration in the circulation were measured using Multi-collector Inductively-Coupled Plasma Mass Spectrometry and Atomic Absorption Spectroscopy, respectively. The physiologic requirement for iron during pregnancy was then calculated by the formula derived from our previously published work.ResultsThe mean physiologic requirement for iron in the 11 subjects, across their entire pregnancies, was 3.05 mg.d- 1 in total and 44.0 μg.kg- 1.d- 1 after adjustment for body mass. The physiologic requirements for iron in the first, second, and third trimesters were 2.04 mg.d- 1, 3.26 mg.d- 1, and 4.13 mg.d- 1, respectively. When adjusted for body mass, the physiologic requirements for iron in different trimesters were 32.3 μg.kg- 1.d- 1, 46.9 μg.kg- 1.d- 1, and 55.7 μg.kg- 1.d- 1, respectively.ConclusionWe preliminarily explored the physiologic requirement for iron in pregnant women. The data demonstrated that pregnant women needed about twice iron than non-pregnant women. This research may be helpful for the design of future studies and the modification of iron DRIs.Trial registrationChiCTR, ChiCTR-OCH-14004302. Registered 14 February 2014, http://www.chictr.org.cn/showproj.aspx?proj=5267.

Dataset Information

A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data.

Publications

A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data.

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