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Advances in stable isotope tracer methodology part 1: hepatic metabolism via isotopomer analysis and postprandial lipolysis modeling
  1. Cecilia Diniz Behn1,2,
  2. Jin Eunsook3,
  3. Kate Bubar1,
  4. Craig Malloy3,
  5. Elizabeth J Parks4,
  6. Melanie Cree-Green2,5
  1. 1 Applied Mathematics and Statistics, Colorado School of Mines, Golden, Colorado, USA
  2. 2 Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA
  3. 3 Advanced Imaging Research Center, UT Southwestern Medical, Dallas, Texas, USA
  4. 4 Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA
  5. 5 Pediatric Endocrinology, Children’s Hospital Colorado, Aurora, Colorado, USA
  1. Correspondence to Dr Melanie Cree-Green, University of Colorado Denver School of Medicine, Aurora, Colorado 80045-2581, USA; Melanie.Green{at}childrenscolorado.org

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.

  • liver
  • research design
  • adipose tissue
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Footnotes

  • Contributors CDB, JE and MC-G researched the data wrote the manuscript. KB, CM, EJP researched the data and edited the manuscript.

  • Funding JE: NIH DK099289; CM: NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB) P41 EB015908; MC-G: NIH BIRCWH K12HD057022, NIH K23DK107871, Children’s Hospital Colorado, Doris Duke Foundation FCRS 2015212; NIH/NCATS Colorado CTSA Grant Number UL1 TR002535. The contents are the authors’ sole responsibility and do not necessarily represent official NIH views.

  • Disclaimer MC-G has received product from AminoCorp, LLC.

  • Competing interests Yes, there are competing interests for one or more authors and I have provided a Competing Interests statement in my manuscript.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Patient consent for publication Not requred.

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