Metabolite exchange between mammalian organs quantified in pigs
Open accessAbstract
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.
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Recent work has found that different tissues in the body have distinct fuel preferences, raising the possibility that the source of acetyl-CoA generation is dependent on cell type and cell state.
“While the mechanisms dictating a cell’s preferred source of acetyl-CoA are not well understood, recent work has found that different tissues in the body have distinct fuel preferences (44), raising the possibility that the source of acetyl-CoA generation is dependent on cell type and cell state.”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [44]
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- Authors
- 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.
- Affiliations
- Princeton University (US)
- University of Cambridge (GB)
- University of Pennsylvania (US)
- Corresponding author
- Rabinowitz, Joshua D.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 30
- Issue
- 3
- Pages
- 594-606.e3
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6726553
- OpenAlex
- W2954321663
- Cited by
- 256
- References
- 54
- Citations by year
- 2026: 26 · 2025: 31 · 2024: 40 · 2023: 56 · 2022: 35 · 2021: 42 · 2020: 21 · 2019: 5
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Update notices
- erratum (2022-09-06)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- American Diabetes Association (1-17-PDF-076, 1DP1DK113643)
- NIH (K99DK117066)
- Diabetes Research Center (P30 DK019525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- arteriovenous differences, organ metabolism, liver, kidney, glucose metabolism, amino acid metabolism, fatty acid oxidation, citrate metabolism, lactate oxidation, redox homeostasis, nucleotide release, fasting state, porcine model
- MeSH terms
- Amino Acids, Animals, Arteries, Blood Glucose, Fasting, Fatty Acids, Intestinal Mucosa, Kidney, Liver, Male, Mice, Inbred C57BL, Pancreas, Spleen, Swine, Veins, Pyruvic Acid, Citric Acid, Lactic Acid, Mice
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