RT Journal Article
SR Electronic
T1 Quantitative fluxomics of circulating metabolites
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.02.973669
DO 10.1101/2020.03.02.973669
A1 Sheng Hui
A1 Alexis J. Cowan
A1 Xianfeng Zeng
A1 Lifeng Yang
A1 Tara TeSlaa
A1 Xiaoxuan Li
A1 Caroline Bartman
A1 Zhaoyue Zhang
A1 Cholsoon Jang
A1 Lin Wang
A1 Wenyun Lu
A1 Jennifer Rojas
A1 Joseph Baur
A1 Joshua D. Rabinowitz
YR 2020
UL http://biorxiv.org/content/early/2020/03/03/2020.03.02.973669.abstract
AB Mammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting both for circulatory metabolic cycles and tissue TCA inputs, across fed and fasted mice on either high carbohydrate or ketogenic diet. We find that a majority of circulating carbon flux is carried by two major cycles: glucose-lactate and triglyceride-glycerol-fatty acid. Futile cycling through these pathways is prominent when dietary content of the associated nutrients is low, rendering internal metabolic activity robust to food choice. The presented in vivo flux quantification methods are broadly applicable to different physiological and disease states.