Systems-level quantitative analysis of inter-organ metabolite exchange in pigs

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, while 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 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.