Myonuclear accretion is a determinant of exercise-induced remodeling in skeletal muscle
- Cincinnati Children's Hospital Medical Center, United States
- University of Cincinnati College of Medicine, United States
- The Jackson Laboratory, United States
Abstract
Skeletal muscle adapts to external stimuli such as increased work. Muscle progenitors (MPs) control muscle repair due to severe damage, but the role of MP fusion and associated myonuclear accretion during exercise are unclear. While we previously demonstrated that MP fusion is required for growth using a supra-physiological model (1), questions remained about the need for myonuclear accrual during muscle adaptation in a physiological setting. Here, we developed a high-intensity interval training (HIIT) protocol and assessed the importance of MP fusion. In 8 month-old mice, HIIT led to progressive myonuclear accretion throughout the protocol, and functional muscle hypertrophy. Abrogation of MP fusion at the onset of HIIT resulted in exercise intolerance and fibrosis. In contrast, ablation of MP fusion 4 weeks into HIIT, preserved exercise tolerance but attenuated hypertrophy. We conclude that myonuclear accretion is required for different facets of exercise-induced adaptive responses, impacting both muscle repair and hypertrophic growth.
Data availability
All data generated in this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institutes of Health (R01AR068286)
- Douglas P Millay
Pew Charitable Trusts
- Douglas P Millay
National Institutes of Health (R01AG059605)
- Douglas P Millay
National Institutes of Health (R01AR060636)
- Se-Jin Lee
National Institutes of Health (R01HL130356)
- Sakthivel Sadayappan
National Institutes of Health (R01HL105826)
- Sakthivel Sadayappan
National Institutes of Health (R01AR067279)
- Sakthivel Sadayappan
National Institutes of Health (RO1/R56HL139680)
- Sakthivel Sadayappan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Andrew Brack, University of California, San Francisco, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the Cincinnati Children's Hospital Medical Center.
Version history
- Received: January 7, 2019
- Accepted: April 22, 2019
- Accepted Manuscript published: April 23, 2019 (version 1)
- Version of Record published: May 2, 2019 (version 2)
- Version of Record updated: May 14, 2019 (version 3)
Copyright
© 2019, Goh et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Myonuclear accretion is a determinant of exercise-induced remodeling in skeletal muscle
eLife 8:e44876.
https://doi.org/10.7554/eLife.44876
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