# Exercise-induced skeletal muscle exosomes promote adipocyte lipolysis

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $403,134

## Abstract

Summary
Exosomes are small extracellular vesicles that have emerged over the past few years as novel mediators of
intercellular communication. We recently reported that exosomes released from activated skeletal muscle stem
cells regulate extracellular matrix remodeling during muscle hypertrophy through the transport of skeletal
muscle-specific miR-206 to fibroblasts. The discovery of this novel role for muscle stem cells inspired us to
further explore if exosomes are released from muscle cells in response to resistance exercise and, if so, their
impact on target tissues. Based on preliminary data, we hypothesize that enhanced adrenergic signaling in
adipose tissue in response to resistance exercise is mediated in part by exosomal muscle-specific miR-1
activation of β3-adrenergic receptor (β3-AR) expression. In particular, we have developed a working model in
which exercise causes skeletal muscle cells to release exosomes containing muscle-specific miR-1 that
transport miR-1 to adipocytes. As a result, CAATT/enhancer binding protein alpha (C/EBPα) activates β3-AR
gene expression through miR-1-mediated repression of AP-2α, thereby enhancing catecholamine sensitivity of
adipocytes and promoting the release of fatty acids and glycerol into the circulation as the result of increased
lipolysis. The purpose of the proposed studies is to test our working model by pursuing the following aims in
both mice and humans: Aim 1: Determine if exercise-induced exosomal miR-1 enhances adipocyte adrenergic
signaling through activation of β3-AR expression; Aim 2: Determine if human skeletal muscle fiber-derived
exosomes directly promote adipocyte lipolysis through enhanced β-adrenergic signaling; Aim 3: Determine if
an acute bout of resistance exercise in humans promotes miR-1-mediated adipocyte lipolysis. Our preliminary
data provide the first evidence demonstrating that resistance exercise-induced exosomes mediate the
beneficial effect of exercise on adipose tissue metabolism. A better understanding of the role of exosomes in
the systemic adaptations that occur in response to resistance exercise are expected to provide the
fundamental knowledge necessary to use exosomes as a platform for the delivery of exercise mimetics to treat
obesity.

## Key facts

- **NIH application ID:** 9983679
- **Project number:** 5R01DK119619-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** JOHN Joseph MCCARTHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,134
- **Award type:** 5
- **Project period:** 2018-09-19 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983679

## Citation

> US National Institutes of Health, RePORTER application 9983679, Exercise-induced skeletal muscle exosomes promote adipocyte lipolysis (5R01DK119619-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9983679. Licensed CC0.

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