Title | Quantitative Fluxomics of Circulating Metabolites. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Hui, 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 |
Journal | Cell Metab |
Volume | 32 |
Issue | 4 |
Pagination | 676-688.e4 |
Date Published | 2020 Oct 06 |
ISSN | 1932-7420 |
Keywords | Animals, Citric Acid Cycle, Fatty Acids, Glucose, Glycerol, Lactic Acid, Mice, Mice, Inbred C57BL, Triglycerides |
Abstract | <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> |
DOI | 10.1016/j.cmet.2020.07.013 |
Alternate Journal | Cell Metab |
PubMed ID | 32791100 |
PubMed Central ID | PMC7544659 |
Grant List | S10 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 |