Metabolite Exchange between Mammalian Organs Quantified in Pigs

Cell Metab. 2019 Sep 3;30(3):594-606.e3. doi: 10.1016/j.cmet.2019.06.002. Epub 2019 Jun 27.


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.

Keywords: circulating metabolite; flux; fuel; inter-organ exchange; isotope tracing; mammalian organ-specific metabolism; metabolomics; pig; tissue; uptake and release.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / blood
  • Animals
  • Arteries
  • Blood Glucose
  • Citric Acid / blood
  • Fasting / blood
  • Fatty Acids / blood
  • Intestinal Mucosa / blood supply
  • Intestinal Mucosa / metabolism
  • Kidney / blood supply
  • Kidney / metabolism*
  • Lactic Acid / blood
  • Liver / blood supply
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pancreas / blood supply
  • Pancreas / metabolism
  • Pyruvic Acid / blood
  • Spleen / blood supply
  • Spleen / metabolism
  • Swine / metabolism*
  • Veins


  • Amino Acids
  • Blood Glucose
  • Fatty Acids
  • Citric Acid
  • Lactic Acid
  • Pyruvic Acid