# DMGV and the AGXT2 pathway in chronic exercise-induced cardiometabolic adaptations.

> **NIH NIH K23** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $170,224

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal details a five-year translational research training program for mentored career development in
molecular profiling, exercise physiology and trial conduct. The candidate is a recently appointed Cardiology
faculty member at Beth Israel Deaconess Medical Center and the outlined proposal builds on the candidate’s
background in cardiovascular prevention and exercise physiology to provide three new domains of expertise –
metabolomics, genetics, and exercise clinical trials. The applicant’s development will occur through a blend of
laboratory training, didactic courses, and scientific conferences. The candidate’s mentor is a recognized leader
in molecular profiling, exercise science, and cardiometabolic disease. The additional mentorship team has a
distinguished mentoring record and vast expertise in metabolomics, genetics and exercise science.
We recently identified a novel plasma metabolite, Dimethylguanidino valeric acid (DMGV) that is a very early
marker of cardiometabolic disease and participant in a biochemical pathway (AGXT2) relevant to exercise
responsiveness and cardiovascular disease. In recently published human data, we found that DMGV levels
decreased after 20 weeks of aerobic exercise training (ET), however individuals with higher baseline levels of
DMGV demonstrated attenuated improvements in lipid traits and insulin sensitivity after completing ET. The
applicant now seeks to extend these studies by relating DMGV levels, and additional AGXT2 pathway
intermediates (e.g. BAIBA, ADMA, glycine) to exercise-induced cardiovascular (e.g. maximal oxygen uptake
[VO2max] and blood pressure) adaptations (Aim 1). Further, the applicant will apply unbiased metabolomics
techniques to identify novel biochemical pathways related to exercise responsiveness (Aim 2). Finally, the
applicant will identify genetic determinants of relevant metabolites identified in Aim 2 by interrogating large,
population-based cohorts with existing genetics and metabolomics data, and integrate findings with long-term
health outcomes to identify novel biochemical pathways involved in exercise and cardiometabolic health (Aim
3). In parallel, the applicant will integrate the same metabolomics techniques with cardiac MRI data in subjects
with metabolic syndrome in order to characterize subclinical cardiac dysfunction, and design an exercise
clinical trial in this population (Aim 4) as part of an R01-level award and transition to independence.
Regular exercise leads to improvements in cardiometabolic health, however significant inter-individual
differences exist and, further, the molecular underpinnings of regular exercise’s salutary effects remain poorly
defined. This proposal will provide the applicant with the required training and expertise in molecular profiling,
exercise physiology, and clinical trials in order to study chronic exercise adaptation in healthy subjects.
Ultimately, this work will lay the foundation for future investigation...

## Key facts

- **NIH application ID:** 10055004
- **Project number:** 1K23HL150327-01A1
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Jeremy Robbins
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $170,224
- **Award type:** 1
- **Project period:** 2020-07-10 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055004

## Citation

> US National Institutes of Health, RePORTER application 10055004, DMGV and the AGXT2 pathway in chronic exercise-induced cardiometabolic adaptations. (1K23HL150327-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10055004. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*