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Endotoxemia induces an early differential metabolic response in the heart and liver as determined by metabolomic analysis

Introduction

Sepsis induces a hypermetabolic state and impairs energy metabolism. In this preliminary small animal study, we used recently developed metabolomics technology to test the hypothesis that metabolic shifts in glucose and amino acid metabolism in the heart and liver occur during the onset of endotoxemia.

Methods

Sepsis was modeled in C57BL/6 mice via administration of lipopolysaccharide (LPS) (intraperitoneally, 40 mg/kg). Five hours post LPS, the left lobe of the liver and the heart were harvested. High-throughput capillary electrophoresis–mass spectrometry was used to identify and quantify metabolite levels based on their unique mass/charge ratio. The advantage of this metabolomics approach is that over 1,000 charged species can be detected in a single sample, generating a unique metabolic profile or readout.

Results

Figure 1 shows relative changes in glucose and glycolytic metabolites, Kreb's cycle intermediates, NADH, ATP and amino acids between 5-hour LPS (n = 2) and control mice (n = 2). Metabolomic analysis suggested that endotoxemia caused an early increase in glucose metabolism in the heart, but a decrease in the liver. NADH levels increased in the liver, but not the heart, while ATP levels decreased in both the liver and the heart. Amino acid levels increased in the liver, with the exception of alanine and glycine, but were more variable in the heart.

Figure 1
figure1

Metabolic profiles for glucose (left) and amino acid (right) metabolism.

Conclusion

Five hours after LPS administration, we found differential glucose and amino acid metabolism in the heart and liver, indicating that profound shifts in metabolism occurred during the onset of endotoxemia.

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Bateman, R., Ohmura, M., Nagahata, Y. et al. Endotoxemia induces an early differential metabolic response in the heart and liver as determined by metabolomic analysis. Crit Care 12, P395 (2008). https://doi.org/10.1186/cc6616

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Keywords

  • NADH
  • Amino Acid Level
  • Amino Acid Metabolism
  • Left Lobe
  • Metabolomic Analysis