Metabolite Exchange between Mammalian Organs Quantified in Pigs.

TitleMetabolite Exchange between Mammalian Organs Quantified in Pigs.
Publication TypeJournal Article
Year of Publication2019
AuthorsJang, C, Hui, S, Zeng, X, Cowan, AJ, Wang, L, Chen, L, Morscher, RJ, Reyes, J, Frezza, C, Hwang, HYoung, Imai, A, Saito, Y, Okamoto, K, Vaspoli, C, Kasprenski, L, Zsido, GA, Gorman, JH, Gorman, RC, Rabinowitz, JD
JournalCell Metab
Volume30
Issue3
Pagination594-606.e3
Date Published2019 09 03
ISSN1932-7420
KeywordsAmino Acids, Animals, Arteries, Blood Glucose, Citric Acid, Fasting, Fatty Acids, Intestinal Mucosa, Kidney, Lactic Acid, Liver, Male, Mice, Mice, Inbred C57BL, Pancreas, Pyruvic Acid, Spleen, Swine, Veins
Abstract

<p>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.</p>

DOI10.1016/j.cmet.2019.06.002
Alternate JournalCell Metab
PubMed ID31257152
PubMed Central IDPMC6726553
Grant ListDP1 DK113643 / DK / NIDDK NIH HHS / United States
K99 DK117066 / DK / NIDDK NIH HHS / United States
MC_UU_12022/6 / / Medical Research Council / United Kingdom
P30 DK019525 / DK / NIDDK NIH HHS / United States