Metabolite Exchange between Mammalian Organs Quantified in Pigs

• Published in: Cell metabolism 2019-09, Vol.30 (3), p.594-606.e3
• Main Authors: Jang, Cholsoon, Hui, Sheng, Zeng, Xianfeng, Cowan, Alexis J., Wang, Lin, Chen, Li, Morscher, Raphael J., Reyes, Jorge, Frezza, Christian, Hwang, Ho Young, Imai, Akito, Saito, Yoshiaki, Okamoto, Keitaro, Vaspoli, Christine, Kasprenski, Loewe, Zsido, Gerald A., Gorman, Joseph H., Gorman, Robert C., Rabinowitz, Joshua D.
• Format: Article
• Language: English
• Subjects: Amino Acids - blood; Animals; Arteries; Blood Glucose; circulating metabolite; Citric Acid - blood; Fasting - blood; Fatty Acids - blood; flux; fuel; inter-organ exchange; Intestinal Mucosa - blood supply; Intestinal Mucosa - metabolism; isotope tracing; Kidney - blood supply; Kidney - metabolism; Lactic Acid - blood; Liver - blood supply; Liver - metabolism; Male; mammalian organ-specific metabolism; metabolomics; Mice; Mice, Inbred C57BL; Pancreas - blood supply; Pancreas - metabolism; pig; Pyruvic Acid - blood; Spleen - blood supply; Spleen - metabolism; Swine - metabolism; tissue; uptake and release; Veins
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2019.06.002

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. [Display omitted] •A systems-level atlas of organ-specific metabolite production and consumption•700 quantitative measurements of organ-specific uptake or excretion•Kidneys burn circulating citrate and net-oxidize lactate to pyruvate•Liver preferentially consumes unsaturated over saturated fatty acids 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.