# Octopamine controls adaptation to endurance exercise in Drosophila

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2021 · $338,800

## Abstract

Octopamine controls adaptation to endurance exercise in Drosophila
Abstract
Exercise is widely recognized as a powerful intervention against metabolic dysfunction and age-related
disease. However, many patients are unable to exercise for extended periods due to illness, injury or lifestyle
factors. Furthermore, individual genetic differences prevent some individuals from receiving the full benefits of
exercise. Here, we propose to use the fruit fly Drosophila as a genetic model to identify specific genetic
pathways that account for individual differences in exercise response. We have developed the first endurance
exercise platform for Drosophila. Using this paradigm, we have discovered that activation of the neurons that
secrete the noradrenergic amine octopamine is both necessary and sufficient to provide the benefits of
exercise to sedentary flies. We have also identified differential octopamine levels as the reason why female
flies have a deficient exercise response in comparison to males. Here, we propose to identify the downstream
mechanism by which octopamine provides these benefits. To do this, we will take advantage of the genetic
tools available in the fruit fly model to pursue the following aims. First, we will identify tissue-specific
requirements for octopamine receptors during exercise using tissue-specific, inducible knockdowns. Second,
we will identify the mechanistic targets for increased excitability in male octopaminergic neurons using single-
cell RNAseq to identify sex-specific transcripts activated by exercise. Third, we will identify the mechanistic
source and requirement for neural plasticity of octopaminergic neurons during chronic exercise using
fluorescent double labelling and confocal microscopy. Because mammals are known to upregulate secretion of
the octopamine-like molecule norepinephrine during exercise, we expect the mechanisms we find to be
conserved in mammals, including humans. These findings will open the way to provide metabolic benefits of
exercise to sedentary patients through pharmacology or neural stimulation.

## Key facts

- **NIH application ID:** 10201508
- **Project number:** 5R01AG059683-04
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Robert John Wessells
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $338,800
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201508

## Citation

> US National Institutes of Health, RePORTER application 10201508, Octopamine controls adaptation to endurance exercise in Drosophila (5R01AG059683-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201508. Licensed CC0.

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