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Advances in stable isotope tracer methodology part 1: hepatic metabolism via isotopomer analysis and postprandial lipolysis modeling.

ABSTRACT: Stable isotope tracers have been used to gain an understanding of integrative animal and human physiology. More commonly studied organ systems include hepatic glucose metabolism, lipolysis from adipose tissue, and whole body protein metabolism. Recent improvements in isotope methodology have included the use of novel physiologic methods/models and mathematical modeling of data during different physiologic states. Here we review some of the latest advancements in this field and highlight future research needs. First we discuss the use of an oral [U-¹³C₃]-glycerol tracer to determine the relative contribution of glycerol carbons to hepatic glucose production after first cycling through the tricarboxylic acid cycle, entry of glycerol into the pentose phosphate pathway or direct conversion of glycerol into the glucose. Second, we describe an adaptation of the established oral minimal model used to define postprandial glucose dynamics to include glycerol dynamics in an oral glucose tolerance test with a [²H₅]-glycerol tracer to determine dynamic changes in lipolysis. Simulation results were optimized when parameters describing glycerol flux were determined with a hybrid approach using both tracer-based calculations and constrained parameter optimization. Both of these methodologies can be used to expand our knowledge of not only human physiology, but also the effects of various nutritional strategies and medications on metabolism.

SUBMITTER: Diniz Behn C

PROVIDER: S-EPMC7372575 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Advances in stable isotope tracer methodology part 1: hepatic metabolism via isotopomer analysis and postprandial lipolysis modeling.

Diniz Behn Cecilia C Jin Eunsook S ES Bubar Kate K Malloy Craig C Parks Elizabeth J EJ Cree-Green Melanie M

Journal of investigative medicine : the official publication of the American Federation for Clinical Research 20190924 1

Stable isotope tracers have been used to gain an understanding of integrative animal and human physiology. More commonly studied organ systems include hepatic glucose metabolism, lipolysis from adipose tissue, and whole body protein metabolism. Recent improvements in isotope methodology have included the use of novel physiologic methods/models and mathematical modeling of data during different physiologic states. Here we review some of the latest advancements in this field and highlight future r ...[more]

PMID: 31554675

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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.

Project description:Background:Iron nutrition is important for the health of women of reproductive age, and defining the physiologic requirement for iron can help them accurately plan the iron intake. However, research on the physiologic requirement for iron in women is insufficient worldwide. This study aimed to further improve the methodology and get more precise data for the physiological requirements for iron in women of reproductive age on the basis of our previous study. Method:Sixty-one women of reproductive age who had not been pregnant before and during the whole study were included from Hebei province, China in 2015. Each subject participated in a 2-week metabolic trial with consuming 50?mg of the stable isotope 58Fe, and were then followed for ~?800?days. 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. The physiologic requirement for iron in women of reproductive age was then calculated. Results:The average iron circulation rate was 80.4%, and the steady period started from about 1?year. The average physiological requirement for iron of 21 subjects obtained by formula calculation was 1.55?mg/d and 23.63??g.kg-?1.d-?1 after adjustment for body mass, and that of 33 subjects obtained by linear regression was 1.29?mg/d, 20.98??g.kg-?1.d-?1 after adjustment for body mass. The results by two methods showed no significant difference. The EAR and RNI calculated from this results was 11-13?mg/d and 15-18?mg/d, respectively, both of which were slightly lower than the recommended value in Chinese Dietary Reference Intake (2013). Conclusion:The physiological requirements for iron in women of reproductive age were in accordance with other studies, while the EAR and RNI calculated from which were slightly lower than Chinese present recommended value. Trial registration:ChiCTR, ChiCTR-OCH-14004302. Registered 14 February 2014, http://www.chictr.org.cn/enindex.aspx.

Dataset Information

Advances in stable isotope tracer methodology part 1: hepatic metabolism via isotopomer analysis and postprandial lipolysis modeling.

Publications

Advances in stable isotope tracer methodology part 1: hepatic metabolism via isotopomer analysis and postprandial lipolysis modeling.

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