Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice
- University of Wisconsin-Madison, United States
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)
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Data from: Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged miceDryad Digital Repository, doi:10.5061/dryad.x95x69pkt.
Article and author information
Author details
Priya Balasubramanian
Rozalyn M Anderson
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.
Reviewing Editor
- Pankaj Kapahi, Buck Institute for Research on Aging, 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 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
Version history
- Received: June 15, 2021
- Preprint posted: September 17, 2021 (view preprint)
- Accepted: March 15, 2022
- Accepted Manuscript published: March 17, 2022 (version 1)
- Version of Record published: March 29, 2022 (version 2)
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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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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