Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice
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 p...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/71282 |
| _version_ | 1811252185369935872 |
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| author | Priya Balasubramanian Anne E Schaar Grace E Gustafson Alex B Smith Porsha R Howell Angela Greenman Scott Baum Ricki J Colman Dudley W Lamming Gary M Diffee Rozalyn M Anderson |
| author_facet | Priya Balasubramanian Anne E Schaar Grace E Gustafson Alex B Smith Porsha R Howell Angela Greenman Scott Baum Ricki J Colman Dudley W Lamming Gary M Diffee Rozalyn M Anderson |
| author_sort | Priya Balasubramanian |
| collection | DOAJ |
| description | 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 one 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. |
| first_indexed | 2024-04-12T16:31:04Z |
| format | Article |
| id | doaj.art-70070234940c48fc8d99e9a3f893e406 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:31:04Z |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-70070234940c48fc8d99e9a3f893e4062022-12-22T03:25:08ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.71282Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged micePriya Balasubramanian0https://orcid.org/0000-0003-0912-5363Anne E Schaar1Grace E Gustafson2https://orcid.org/0000-0001-8343-4493Alex B Smith3https://orcid.org/0000-0002-2615-8899Porsha R Howell4Angela Greenman5Scott Baum6Ricki J Colman7Dudley W Lamming8https://orcid.org/0000-0002-0079-4467Gary M Diffee9Rozalyn M Anderson10https://orcid.org/0000-0002-0864-7998Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesDepartment of Kinesiology, University of Wisconsin-Madison, Madison, United StatesWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, United StatesWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, United States; Department of Cell and Regenerative Biology, University of Wisconsin, Madison, United StatesDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States; Geriatric Research, Education, and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, United StatesDepartment of Kinesiology, University of Wisconsin-Madison, Madison, United StatesDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesThe 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 one 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.https://elifesciences.org/articles/71282agingmusclemitochondriaadiponectinPGC-1aAMPK |
| spellingShingle | Priya Balasubramanian Anne E Schaar Grace E Gustafson Alex B Smith Porsha R Howell Angela Greenman Scott Baum Ricki J Colman Dudley W Lamming Gary M Diffee Rozalyn M Anderson Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice eLife aging muscle mitochondria adiponectin PGC-1a AMPK |
| title | Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice |
| title_full | Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice |
| title_fullStr | Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice |
| title_full_unstemmed | Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice |
| title_short | Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice |
| title_sort | adiponectin receptor agonist adiporon improves skeletal muscle function in aged mice |
| topic | aging muscle mitochondria adiponectin PGC-1a AMPK |
| url | https://elifesciences.org/articles/71282 |
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