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Quantitative flux analysis in mammals

Nature Metabolism volume 3, pages 896–908 (2021)Cite this article

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Abstract

Altered metabolic activity contributes to the pathogenesis of a number of diseases, including diabetes, heart failure, cancer, fibrosis and neurodegeneration. These diseases, and organismal metabolism more generally, are only partially recapitulated by cell culture models. Accordingly, it is important to measure metabolism in vivo. Over the past century, researchers studying glucose homeostasis have developed strategies for the measurement of tissue-specific and whole-body metabolic activity (pathway fluxes). The power of these strategies has been augmented by recent advances in metabolomics technologies. Here, we review techniques for measuring metabolic fluxes in intact mammals and discuss how to analyse and interpret the results. In tandem, we describe important findings from these techniques, and suggest promising avenues for their future application. Given the broad importance of metabolism to health and disease, more widespread application of these methods holds the potential to accelerate biomedical progress.

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Fig. 1: Mammalian metabolic fluxes.
Fig. 2: Measuring net tissue fluxes using arteriovenous sampling.
Fig. 3: Measuring circulatory turnover flux using tracer infusion.
Fig. 4: Pre-steady-state versus steady-state measurements of tissue metabolite labelling.
Fig. 5: Measuring sources of tissue metabolites using tracer infusion.

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Acknowledgements

We thank Yihui Shen, Wenyun Lu, Michael Neinast, Asael Roichman and other members of the Rabinowitz laboratory for helpful discussion. This work was supported by NIH Pioneer award 5DP1DK113643, Diabetes Research Center grant P30 DK019525 and Paul G. Allen Family Foundation grant 0034665 to J.D.R., NIH fellowship F32DK118856 to T.T. and Damon Runyon Cancer Research Foundation fellowship DRG-2373-19 to C.R.B.

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Authors and Affiliations

  1. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA

    Caroline R. Bartman, Tara TeSlaa & Joshua D. Rabinowitz

  2. Department of Chemistry, Princeton University, Princeton, NJ, USA

    Caroline R. Bartman, Tara TeSlaa & Joshua D. Rabinowitz

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  1. Caroline R. Bartman
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  2. Tara TeSlaa
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  3. Joshua D. Rabinowitz
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C.R.B., T.T. and J.D.R. conceived and wrote the review.

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Correspondence to Joshua D. Rabinowitz.

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The authors declare no competing interests.

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Peer review information Nature Metabolism thanks Julian Griffin and Elizabeth Want for their contribution to the peer review of this work. Primary Handling Editor: George Caputa.

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Bartman, C.R., TeSlaa, T. & Rabinowitz, J.D. Quantitative flux analysis in mammals. Nat Metab 3, 896–908 (2021). https://doi.org/10.1038/s42255-021-00419-2

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