# A biochemical roadmap of exercise signal

> **NIH NIH U24** · BROAD INSTITUTE, INC. · 2024 · $1

## Abstract

Project Summary
Exercise is an effective intervention for both the prevention and treatment of cardiometabolic diseases, but the
mechanistic underpinnings of the health benefits of exercise remain incompletely defined. Recent work
highlights the importance of inter-organ circuits in mediating healthful exercise responses. We identified β-
aminoisobutyric acid (BAIBA) as a novel small molecule “myokine” that increases the expression of brown
adipocyte-specific genes in vitro, and improves glucose disposal and decreases weight gain in mice. In
humans, plasma BAIBA concentrations are increased with chronic exercise and demonstrate a strong inverse
association with metabolic risk factors. Further, related efforts by our group have positioned us as leaders in
characterizing within- and between-tissue molecular responses to exercise and dietary interventions.
These experiences, coupled with the high translational relevance of the research problem, motivated our
participation in the first phase of the MoTrPAC initiative. Our team was built upon existing collaborations
between Duke, Harvard and the Broad Institute with complementary strengths in metabolomics and proteomics
technologies and decades of experience in cardiometabolic research. During the initial MoTrPAC funding
period, we provided a deep menu of analytical tools for targeted and non-targeted metabolomics, protein
profiling, and the analysis of key protein post-translational modifications. Group members were deeply involved
in the animal and pre-COVID biochemical profiling efforts, in collaborations with other Chemical Analysis Sites
(CAS) and the Bioinformatics Core to harmonize work flows, and in the working groups necessary to integrate
the data. We have also played key roles in associated scholarly activities and in developing the next
generation of translational investigators focused on exercise science.
An additional distinction of our team is the ability to integrate new findings from MoTrPAC with ongoing
genomic, proteomic and metabolomic analyses in large human cohorts and other exercise studies led by our
investigators. We hypothesize that integrating the metabolomic and proteomic profiles of human tissues and
blood during exercise with genetics and detailed human phenotyping will provide novel insights into the inter-
organ circuits and within-organ responses that mediate its salutary effects. We are deeply committed to the
notion that all data generated by this multi-disciplinary consortium will be made rapidly available to the
scientific community. Importantly, all four leaders of this proposed core (Carr, Clish, Gerszten and Newgard)
have strong track records in the use of metabolomics and proteomics tools for the identification of novel
cardiometabolic regulatory and disease mechanisms. These experiences position our CAS as one that can
have maximal impact on the generation, analysis, and interpretation of molecular profiling data in the next
phase of MoTrPAC.

## Key facts

- **NIH application ID:** 10892409
- **Project number:** 2U24DK112340-07
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** STEVEN A CARR
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1
- **Award type:** 2
- **Project period:** 2016-12-14 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892409

## Citation

> US National Institutes of Health, RePORTER application 10892409, A biochemical roadmap of exercise signal (2U24DK112340-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10892409. Licensed CC0.

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