# Metabolism in Action: Quantitative Fluxes in Mammals

> **NIH NIH DP1** · PRINCETON UNIVERSITY · 2020 · $1,134,000

## Abstract

Metabolism in Action: Quantitative Fluxes in Mammals
Abstract
The molecular connections involved in metabolism are the best understood of any major
biochemical network. Nevertheless, metabolic disease remains at epidemic levels, and other
diseases involving aberrant metabolism, such as cancer, continue unabated. A key step
towards addressing these major unmet medical needs is to understand the integrated activity of
metabolic pathways, and their modulation by diet and disease. Despite the recent revitalized
interest in metabolism, systems-level methods for measuring metabolic activity in intact
mammals remain in their infancy.Here I propose to combine isotope tracing, state-of-the-art
metabolomics technology, and computational modeling to reveal metabolic activity at the whole
body level. Labeled nutrients will be infused intravenously into mice, tissues sampled, and
metabolite labeling quantified by liquid chromatography-mass spectrometry. Metabolic pathway
flows (fluxes) consistent with the tracer data will be identified within the context of whole body
metabolic model, which encompasses tissue-specific metabolic activity and exchange of
metabolites between organs via the circulation. The fluxes will also be constrained by
macroscopic measurements like food and oxygen uptake and carbon dioxide and urea excretion
rates, tying our approach to classical physiological measurements. Through these studies, we
will revisit from a quantitative perspective the overall operation of mammalian metabolism.
Anticipated outcomes include enhanced understanding of the sources and consumption routes
of circulating metabolites, discovery of novel metabolic cycles connecting different organs, and
quantitative measurement methods of broad utility for probing disease models. Application of
these methods will reveal disease-specific pathway dysregulation. The overall impact will be a
more holistic and comprehensive understanding of metabolism that enables rational dietary
guidance and therapeutic intervention across a broad spectrum of diseases.

## Key facts

- **NIH application ID:** 9987597
- **Project number:** 5DP1DK113643-05
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** JOSHUA D RABINOWITZ
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,134,000
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987597

## Citation

> US National Institutes of Health, RePORTER application 9987597, Metabolism in Action: Quantitative Fluxes in Mammals (5DP1DK113643-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9987597. Licensed CC0.

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