@article{33695021b90f4617bbb53a89ff9a40c0,
title = "Metabolite Exchange between Mammalian Organs Quantified in Pigs",
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.",
keywords = "circulating metabolite, flux, fuel, inter-organ exchange, isotope tracing, mammalian organ-specific metabolism, metabolomics, pig, tissue, uptake and release",
author = "Cholsoon Jang and Sheng Hui and Xianfeng Zeng and Cowan, {Alexis J.} and Lin Wang and Li Chen and Morscher, {Raphael J.} and Jorge Reyes and Christian Frezza and Hwang, {Ho Young} and Akito Imai and Yoshiaki Saito and Keitaro Okamoto and Christine Vaspoli and Loewe Kasprenski and Zsido, {Gerald A.} and Gorman, {Joseph H.} and Gorman, {Robert C.} and Rabinowitz, {Joshua D.}",
note = "Funding Information: C.J. is a postdoctoral fellow of the American Diabetes Association ( 1-17-PDF-076 ). S.H. is supported by the NIH grant K99DK117066 . This work was supported by NIH Pioneer award 1DP1DK113643 and Diabetes Research Center grant P30 DK019525 . We thank members of the Rabinowitz lab for scientific discussions. Funding Information: C.J. is a postdoctoral fellow of the American Diabetes Association (1-17-PDF-076). S.H. is supported by the NIH grant K99DK117066. This work was supported by NIH Pioneer award 1DP1DK113643 and Diabetes Research Center grant P30 DK019525. We thank members of the Rabinowitz lab for scientific discussions. C.J. R.J.M. and J.D.R. designed the study. C.J. performed most experiments. S.H. contributed to isotope tracing studies in pigs and mice, modeling, and data analysis. X.Z. contributed to isotope tracing studies in mice, developed the analytical method for SCFA, and collected the SCFA data. A.J.C. contributed to pig experiments and sample preparation. J.R. contributed to the flux analysis. L.W. and L.C. contributed to chemical formula assignment of putative metabolites. C.F. contributed the ideas on kidney cancer. H.Y.H. A.I. Y.S. K.O. C.V. L.K. and G.A.Z. performed pig surgery and blood collection. J.H.G. and R.C.G. provided surgical expertise and intellectual guidance. C.J. and J.D.R. wrote the manuscript. All authors discussed the results and commented on the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = sep,
day = "3",
doi = "10.1016/j.cmet.2019.06.002",
language = "English (US)",
volume = "30",
pages = "594--606.e3",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",
}