Quantitative Fluxomics of Circulating Metabolites.

TitleQuantitative Fluxomics of Circulating Metabolites.
Publication TypeJournal Article
Year of Publication2020
AuthorsHui, S, Cowan, AJ, Zeng, X, Yang, L, TeSlaa, T, Li, X, Bartman, C, Zhang, Z, Jang, C, Wang, L, Lu, W, Rojas, J, Baur, J, Rabinowitz, JD
JournalCell Metab
Date Published2020 Oct 06
KeywordsAnimals, Citric Acid Cycle, Fatty Acids, Glucose, Glycerol, Lactic Acid, Mice, Mice, Inbred C57BL, Triglycerides

<p>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 for both 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.</p>

Alternate JournalCell Metab
PubMed ID32791100
PubMed Central IDPMC7544659
Grant ListS10 OD025098 / OD / NIH HHS / United States
DP1 DK113643 / DK / NIDDK NIH HHS / United States
R00 DK117066 / DK / NIDDK NIH HHS / United States
R50 CA211437 / CA / NCI NIH HHS / United States
P30 DK019525 / DK / NIDDK NIH HHS / United States
F32 DK118856 / DK / NIDDK NIH HHS / United States
K99 DK117066 / DK / NIDDK NIH HHS / United States