1. Cell Biology

Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice

  1. Priya Balasubramanian
  2. Anne E Schaar
  3. Grace E Gustafson
  4. Alex B Smith
  5. Porsha R Howell
  6. Angela Greenman
  7. Scott Baum
  8. Ricki J Colman
  9. Dudley W Lamming
  10. Gary M Diffee
  11. Rozalyn M Anderson  Is a corresponding author
  1. University of Wisconsin-Madison, United States
https://doi.org/10.7554/eLife.71282
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Cite this article
  1. Priya Balasubramanian
  2. Anne E Schaar
  3. Grace E Gustafson
  4. Alex B Smith
  5. Porsha R Howell
  6. Angela Greenman
  7. Scott Baum
  8. Ricki J Colman
  9. Dudley W Lamming
  10. Gary M Diffee
  11. Rozalyn M Anderson
(2022)
Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice
eLife 11:e71282.
https://doi.org/10.7554/eLife.71282
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Abstract

The loss of skeletal muscle function with age, known as sarcopenia, significantly reduces independence and quality of life and can have significant metabolic consequences. Although exercise is effective in treating sarcopenia it is not always a viable option clinically, and currently there are no pharmacological therapeutic interventions for sarcopenia. Here we show that chronic treatment with pan-adiponectin receptor agonist AdipoRon improved muscle function in male mice by a mechanism linked to skeletal muscle metabolism and tissue remodeling. In aged mice, 6 weeks of AdipoRon treatment improved skeletal muscle functional measures in vivo and ex vivo. Improvements were linked to changes in fiber type, including an enrichment of oxidative fibers, and an increase in mitochondrial activity. In young mice, 6 weeks of AdipoRon treatment improved contractile force and activated the energy sensing kinase AMPK and the mitochondrial regulator PGC-1a (peroxisome proliferator activated receptor gamma coactivator 1 alpha). In cultured cells, the AdipoRon induced stimulation of AMPK and PGC-1a was associated with increased mitochondrial membrane potential, reorganization of mitochondrial architecture, increased respiration, and increased ATP production. Furthermore, the ability of AdipoRon to stimulate AMPK and PGC1a was conserved in nonhuman primate cultured cells. These data show that AdipoRon is an effective agent for the prevention of sarcopenia in mice and indicate that its effects translate to primates, suggesting it may also be a suitable therapeutic for sarcopenia in clinical application.

Data availability

All data generated or analyzed during this experimental study are included in the manuscript and supporting files used to generate figures 1-6 have been deposited to Dryad at URL (https://doi.org/10.5061/dryad.x95x69pkt)

The following data sets were generated

Article and author information

Author details

  1. Priya Balasubramanian

    Department of Medicine, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0912-5363

  2. Anne E Schaar

    Department of Medicine, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Grace E Gustafson

    Department of Medicine, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8343-4493

  4. Alex B Smith

    Department of Medicine, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2615-8899

  5. Porsha R Howell

    Department of Medicine, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Angela Greenman

    Department of Kinesiology, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Scott Baum

    Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Ricki J Colman

    Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Dudley W Lamming

    Department of Medicine, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0079-4467

  10. Gary M Diffee

    Department of Kinesiology, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Rozalyn M Anderson

    Department of Medicine, University of Wisconsin-Madison, Madison, United States
    For correspondence
    rozalyn.anderson@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0864-7998

Funding

U.S. Department of Veterans Affairs (BX003846)

  • Priya Balasubramanian
  • Anne E Schaar
  • Rozalyn M Anderson

U.S. Department of Veterans Affairs (BX004031)

  • Dudley W Lamming

National Institute on Aging (AG040178)

  • Alex B Smith
  • Scott Baum
  • Ricki J Colman
  • Rozalyn M Anderson

National Institute on Aging (AG056771)

  • Dudley W Lamming

National Institutes of Health (AG000213)

  • Anne E Schaar

National Institutes of Health (GM083252)

  • Porsha R Howell

National Institutes of Health (P51OD011106)

  • Scott Baum
  • Ricki J Colman

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 to minimize animal harm and suffering. All animal protocols were approved by the Institutional Animal Care and Use Committee at the University of Wisconsin, Madison on animal protocols #RA-0005-1 and #RA-0007-1

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Priya Balasubramanian
  2. Anne E Schaar
  3. Grace E Gustafson
  4. Alex B Smith
  5. Porsha R Howell
  6. Angela Greenman
  7. Scott Baum
  8. Ricki J Colman
  9. Dudley W Lamming
  10. Gary M Diffee
  11. Rozalyn M Anderson
(2022)
Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice
eLife 11:e71282.
https://doi.org/10.7554/eLife.71282

Share this article

https://doi.org/10.7554/eLife.71282

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