# Metabolic regulation of exercise-induced adaptation in striated muscle

> **NIH NIH F31** · UNIVERSITY OF LOUISVILLE · 2021 · $36,647

## Abstract

Abstract
Aerobic exercise promotes beneficial adaptations in the heart. Previous studies demonstrate that transient
reductions in cardiac glucose catabolism at the level of phosphofructokinase are important for exercise-induced
cardiac growth. Although this finding links changes in metabolism with initiation of growth, the mechanisms by
which glucose metabolism changes during exercise and how metabolism coordinates cardiac growth remain
unclear. Metabolic changes could promote exercise-induced muscle growth in two ways. First, changes in the
levels of glycolytic intermediates during exercise could regulate carbon availability for building block biosynthesis,
which constitutes a material cause for cardiomyocyte hypertrophy. Second, metabolic changes that occur during
exercise could regulate the exercise gene program, which is important for exercise-induced tissue remodeling.
Nevertheless, it has been difficult to disentangle the contribution of these two causes to the adaptations brought
forth by exercise. Addressing these problems requires understanding how metabolism changes both during and
after exercise, and then identifying the metabolic components that modulate cardiomyocyte growth. In this
project, I will test the general hypothesis that high levels of competing substrates such as lactate and fatty acids
prompt ancillary biosynthetic pathway activity in the heart and drive gene programs for cardiac growth. To
understand how glucose metabolism changes in response to exercise or in the presence of competing
substrates, I have standardized deep network tracing methods to measure glucose-derived carbon fate in vivo
using dietary delivery of a 13C6-glucose-containing diet. Specifically, the aims are (1) to define changes in cardiac
glucose metabolism in response to exercise training and (2) to determine how circulating substrates influence
cardiac hypertrophic signaling and gene programs. This research plan will provide training in areas critical to my
growth as a scientist and prepare me for a career in the exercise sciences. The project will provide fresh
perspectives about how metabolism regulates cardiac muscle growth and could identify innovative metabolic
approaches to control tissue remodeling or optimize the cardiovascular benefits of exercise. Importantly, these
studies will integrate our current understanding of striated muscle catabolism with new knowledge of how
anabolism is regulated within muscle tissue.

## Key facts

- **NIH application ID:** 10462474
- **Project number:** 5F31HL154663-02
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Kyle Fulghum
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,647
- **Award type:** 5
- **Project period:** 2020-08-10 → 2023-08-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462474

## Citation

> US National Institutes of Health, RePORTER application 10462474, Metabolic regulation of exercise-induced adaptation in striated muscle (5F31HL154663-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10462474. Licensed CC0.

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