# Epigenomic Remodeling of Metabolism by Exercise through AP-1

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $396,250

## Abstract

Project Summary/Abstract
We want to address how physical exercise remodels metabolism and ameliorates type 2 diabetes. Exercise is
a first-line treatment for type 2 diabetes, and exerts its beneficial effects not only by burning off energy but also
by causing prolonged metabolic changes through epigenomic regulation of gene expression. Nonbiased
identification of key epigenomic players that mediate exercise-induced gene expression changes has not been
attempted. Using global nuclear-run on (GRO-seq) and enhancer RNA (eRNA) as functional enhancer
markers, we identified activation protein-1 (AP-1) as the dominant transcription factors that drive exercise-
induced enhancers in mouse skeletal muscles after bouts of exercise. Loss-of-function screening identified the
pivotal role of JunD, an AP-1 factor, in muscle contraction-induced stress response and metabolic changes in
fully-differentiated primary myotubes. We will address the in vivo function of JunD/AP-1 in exercise-mediated
metabolic remodeling using conditional knockout and overexpression mouse models. We will also characterize
the upstream signals that activates JunD/AP-1, determine the genuine target genes and epigenomic changes
controlled by JunD/AP-1, and address the conservation of the JunD pathway in human exercise physiology.
Together, this work will provide epigenomic insights into the intermediary metabolism system that is shaped by
intermittent exercise during natural evolution. This will lay intellectual groundwork for drug discovery programs
that aim to maximize the metabolic benefit of physical exercise, especially considering that accumulating
epigenome-modifying drugs are available and show promises in treating cancer and many other diseases in
clinical trials.

## Key facts

- **NIH application ID:** 9994280
- **Project number:** 5R01DK111436-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Zheng Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994280

## Citation

> US National Institutes of Health, RePORTER application 9994280, Epigenomic Remodeling of Metabolism by Exercise through AP-1 (5R01DK111436-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9994280. Licensed CC0.

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