Metabolite Exchange between Mammalian Organs Quantified in Pigs

Cholsoon Jang, Sheng Hui, Xianfeng Zeng, Alexis J. Cowan, Lin Wang, Li Chen, Raphael J. Morscher, Jorge Reyes, Christian Frezza, Ho Young Hwang, Akito Imai, Yoshiaki Saito, Keitaro Okamoto, Christine Vaspoli, Loewe Kasprenski, Gerald A. Zsido, Joseph H. Gorman, Robert C. Gorman, Joshua D. Rabinowitz

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Mammalian organs continually exchange metabolites via circulation, but systems-level analysis of this shuttling process is lacking. Here, we compared, in fasted pigs, metabolite concentrations in arterial blood versus draining venous blood from 11 organs. Greater than 90% of metabolites showed arterial-venous differences across at least one organ. Surprisingly, the liver and kidneys released not only glucose but also amino acids, both of which were consumed primarily by the intestine and pancreas. The liver and kidneys exhibited additional unexpected activities: liver preferentially burned unsaturated over more atherogenic saturated fatty acids, whereas the kidneys were unique in burning circulating citrate and net oxidizing lactate to pyruvate, thereby contributing to circulating redox homeostasis. Furthermore, we observed more than 700 other cases of tissue-specific metabolite production or consumption, such as release of nucleotides by the spleen and TCA intermediates by pancreas. These data constitute a high-value resource, providing a quantitative atlas of inter-organ metabolite exchange. Using metabolomics in the arterial blood and draining veins of 11 organs in fasted pigs, Jang et al. map more than 700 cases of organ-specific metabolite production or consumption. The resulting data resource provides a blueprint for the integrative function of mammalian metabolism.

Original languageEnglish (US)
Pages (from-to)594-606.e3
JournalCell Metabolism
Volume30
Issue number3
DOIs
StatePublished - Sep 3 2019

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Keywords

  • circulating metabolite
  • flux
  • fuel
  • inter-organ exchange
  • isotope tracing
  • mammalian organ-specific metabolism
  • metabolomics
  • pig
  • tissue
  • uptake and release

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  • Cite this

    Jang, C., Hui, S., Zeng, X., Cowan, A. J., Wang, L., Chen, L., Morscher, R. J., Reyes, J., Frezza, C., Hwang, H. Y., Imai, A., Saito, Y., Okamoto, K., Vaspoli, C., Kasprenski, L., Zsido, G. A., Gorman, J. H., Gorman, R. C., & Rabinowitz, J. D. (2019). Metabolite Exchange between Mammalian Organs Quantified in Pigs. Cell Metabolism, 30(3), 594-606.e3. https://doi.org/10.1016/j.cmet.2019.06.002