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Quantitative Fluxomics of Circulating Metabolites.

Abstract：

: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.

journal_name

Cell Metab

journal_title

Cell metabolism

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

doi

10.1016/j.cmet.2020.07.013

subject

Has Abstract

pub_date

2020-10-06 00:00:00

pages

676-688.e4

issue

4

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(20)30371-5

journal_volume

32

pub_type

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