1. Developmental Biology
  2. Stem Cells and Regenerative Medicine
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Myonuclear accretion is a determinant of exercise-induced remodeling in skeletal muscle

  1. Qingnian Goh
  2. Tajeong Song
  3. Michael J Petrany
  4. Alyssa AW Cramer
  5. Chengyi Sun
  6. Sakthivel Sadayappan
  7. Se-Jin Lee
  8. Douglas P Millay  Is a corresponding author
  1. Cincinnati Children's Hospital Medical Center, United States
  2. University of Cincinnati College of Medicine, United States
  3. The Jackson Laboratory, United States
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Cite this article as: eLife 2019;8:e44876 doi: 10.7554/eLife.44876

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

  1. Qingnian Goh

    Department of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Tajeong Song

    Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati College of Medicine, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael J Petrany

    Depatment of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alyssa AW Cramer

    Department of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2997-5066
  5. Chengyi Sun

    Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8500-1878
  6. Sakthivel Sadayappan

    Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati College of Medicine, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Se-Jin Lee

    The Jackson Laboratory, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Douglas P Millay

    Depatment of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    For correspondence
    douglas.millay@cchmc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5188-0720

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.

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.

Reviewing Editor

  1. Andrew Brack, University of California, San Francisco, United States

Publication history

  1. Received: January 7, 2019
  2. Accepted: April 22, 2019
  3. Accepted Manuscript published: April 23, 2019 (version 1)
  4. Version of Record published: May 2, 2019 (version 2)
  5. 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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