In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and 13C-Lactate Are Impacted by Tracer Recycling and Equilibrium Assumptions
Summary: Isotope-based assessment of metabolic flux is achieved through a judicious balance of measurements and assumptions. Recent publications debate the validity of key assumptions used to model stable isotope labeling of liver metabolism in vivo. Here, we examine the controversy surrounding esti...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720309712 |
| _version_ | 1819211322377633792 |
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| author | Clinton M. Hasenour Mohsin Rahim Jamey D. Young |
| author_facet | Clinton M. Hasenour Mohsin Rahim Jamey D. Young |
| author_sort | Clinton M. Hasenour |
| collection | DOAJ |
| description | Summary: Isotope-based assessment of metabolic flux is achieved through a judicious balance of measurements and assumptions. Recent publications debate the validity of key assumptions used to model stable isotope labeling of liver metabolism in vivo. Here, we examine the controversy surrounding estimates of liver citric acid cycle and gluconeogenesis fluxes using a flexible modeling platform that enables rigorous testing of standard assumptions. Fasted C57BL/6J mice are infused with [13C3]lactate or [13C3]propionate isotopes, and hepatic fluxes are regressed using models with gradually increasing complexity and relaxed assumptions. We confirm that liver pyruvate cycling fluxes are incongruent between different 13C tracers in models with conventional assumptions. When models are expanded to include more labeling measurements and fewer constraining assumptions, however, liver pyruvate cycling is significant, and inconsistencies in hepatic flux estimates using [13C3]lactate and [13C3]propionate isotopes emanate, in part, from peripheral tracer recycling and incomplete isotope equilibration within the citric acid cycle. |
| first_indexed | 2024-12-23T06:25:14Z |
| format | Article |
| id | doaj.art-1be4c676b4eb46bea35bb7439aab217e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T06:25:14Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1be4c676b4eb46bea35bb7439aab217e2022-12-21T17:57:05ZengElsevierCell Reports2211-12472020-08-01325107986In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and 13C-Lactate Are Impacted by Tracer Recycling and Equilibrium AssumptionsClinton M. Hasenour0Mohsin Rahim1Jamey D. Young2Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USADepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USADepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37235, USA; Corresponding authorSummary: Isotope-based assessment of metabolic flux is achieved through a judicious balance of measurements and assumptions. Recent publications debate the validity of key assumptions used to model stable isotope labeling of liver metabolism in vivo. Here, we examine the controversy surrounding estimates of liver citric acid cycle and gluconeogenesis fluxes using a flexible modeling platform that enables rigorous testing of standard assumptions. Fasted C57BL/6J mice are infused with [13C3]lactate or [13C3]propionate isotopes, and hepatic fluxes are regressed using models with gradually increasing complexity and relaxed assumptions. We confirm that liver pyruvate cycling fluxes are incongruent between different 13C tracers in models with conventional assumptions. When models are expanded to include more labeling measurements and fewer constraining assumptions, however, liver pyruvate cycling is significant, and inconsistencies in hepatic flux estimates using [13C3]lactate and [13C3]propionate isotopes emanate, in part, from peripheral tracer recycling and incomplete isotope equilibration within the citric acid cycle.http://www.sciencedirect.com/science/article/pii/S2211124720309712metabolic flux analysisliver metabolismgluconeogenesiscitric acid cycleanaplerosispyruvate kinase |
| spellingShingle | Clinton M. Hasenour Mohsin Rahim Jamey D. Young In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and 13C-Lactate Are Impacted by Tracer Recycling and Equilibrium Assumptions Cell Reports metabolic flux analysis liver metabolism gluconeogenesis citric acid cycle anaplerosis pyruvate kinase |
| title | In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and 13C-Lactate Are Impacted by Tracer Recycling and Equilibrium Assumptions |
| title_full | In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and 13C-Lactate Are Impacted by Tracer Recycling and Equilibrium Assumptions |
| title_fullStr | In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and 13C-Lactate Are Impacted by Tracer Recycling and Equilibrium Assumptions |
| title_full_unstemmed | In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and 13C-Lactate Are Impacted by Tracer Recycling and Equilibrium Assumptions |
| title_short | In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and 13C-Lactate Are Impacted by Tracer Recycling and Equilibrium Assumptions |
| title_sort | in vivo estimates of liver metabolic flux assessed by 13c propionate and 13c lactate are impacted by tracer recycling and equilibrium assumptions |
| topic | metabolic flux analysis liver metabolism gluconeogenesis citric acid cycle anaplerosis pyruvate kinase |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720309712 |
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