In situ metabolic flux analysis to quantify the liver metabolic response to experimental burn injury

Maria Louisa Izamis, Nripen S. Sharma, Basak Uygun, Robert Bieganski, Nima Saeidi, Yaakov Nahmias, Korkut Uygun, Martin L. Yarmush, Francois Berthiaume*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Trauma such as burns induces a hypermetabolic response associated with altered central carbon and nitrogen metabolism. The liver plays a key role in these metabolic changes; however, studies to date have evaluated the metabolic state of liver using ex vivo perfusions or isotope labeling techniques targeted to specific pathways. Herein, we developed a unique mass balance approach to characterize the metabolic state of the liver in situ, and used it to quantify the metabolic changes to experimental burn injury in rats. Rats received a sham (control uninjured), 20% or 40% total body surface area (TBSA) scald burn, and were allowed to develop a hypermetabolic response. One day prior to evaluation, all animals were fasted to deplete glycogen stores. Four days post-burn, blood flow rates in major vessels of the liver were measured, and blood samples harvested. We combined measurements of metabolite concentrations and flow rates in the major vessels entering and leaving the liver with a steady-state mass balance model to generate a quantitative picture of the metabolic state of liver. The main findings were: (1) Sham-burned animals exhibited a gluconeogenic pattern, consistent with the fasted state; (2) the 20% TBSA burn inhibited gluconeogenesis and exhibited glycolytic-like features with very few other significant changes; (3) the 40% TBSA burn, by contrast, further enhanced gluconeogenesis and also increased amino acid extraction, urea cycle reactions, and several reactions involved in oxidative phosphorylation. These results suggest that increasing the severity of injury does not lead to a simple dose-dependent metabolic response, but rather leads to qualitatively different responses.

Original languageAmerican English
Pages (from-to)839-852
Number of pages14
JournalBiotechnology and Bioengineering
Volume108
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Keywords

  • Hypermetabolism
  • In vivo
  • Liver
  • Metabolic flux analysis
  • Rat
  • Trauma and burns

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