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Publication
In Vivo Estimates of Liver Metabolic Flux Assessed by 13C-Propionate and
13C-Lactate Are Impacted by Tracer Recycling and Equilibrium Assumptions.
Authors Hasenour CM, Rahim M, Young JD
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Cell reports
Year 2020
Date Published 8/1/2020
Volume : Pages 32 : 107986
PubMed Reference 32755580
Abstract 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.





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