Small molecule adiponectin receptor agonist GTDF protects against skeletal muscle atrophy
Abstract
Skeletal muscle atrophy is a debilitating response to several major diseases, muscle disuse and chronic steroid treatment for which currently no therapy is available. Since adiponectin signaling plays key roles in muscle energetics, we assessed if globular adiponectin (gAd) or the small molecule adiponectin mimetic 6-C-β-D-glucopyranosyl-(2S,3S)-(+)-5,7,3',4'-tetrahydroxydihydroflavonol (GTDF) could ameliorate muscle atrophy. Both GTDF and gAd induced C2C12 myoblast differentiation. GTDF and gAd effectively prevented reduction in myotube area and suppressed the expressions of atrophy markers; atrogin-1 and muscle ring finger protein-1 (MuRF1) in models of steroid, cytokine and starvation -induced muscle atrophy. The protective effects of GTDF and gAd were routed through AMPK and AKT activation and thereby stimulation of PPAR gamma coactivator 1α and inhibition of forkhead box O transcription factors. Finally, GTDF and gAd mitigated dexamethasone-induced muscle atrophy in vivo. Together, our results demonstrate that activating adiponectin signaling may be an effective therapeutic strategy against skeletal muscle atrophy.
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ApN counteracted muscle atrophy in rats challenged in vivo by glucocorticoids.
“In addition, ApN counteracted muscle atrophy in rats challenged in vivo by glucocorticoids [115].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [115]
The effects of ApN on steroid-induced atrophy were mediated through activation of AMPK and AKT pathways leading to stimulation of PGC-1α and inhibition of FoxOs.
“These effects were mediated through activation of AMPK and AKT pathways that led to stimulation of PGC-1α and inhibition of FoxOs.”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [115]
ApN mitigates steroid-induced atrophy in vitro in a murine cell line.
“ApN has been found to mitigate steroid-induced atrophy in vitro in a murine cell line.”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [115]
GTDF protected against skeletal muscle atrophy by increasing myoblast differentiation and suppressing atrogin-1 and MuRF1 in models of steroid, cytokine and starvation-induced muscle atrophy.
“GTDF also protected against skeletal muscle atrophy, by increasing myoblast differentiation and suppressing the expressions of atrophy markers, such as atrogin-1 and MuRF1, in models of steroid, cytokine and starvation-induced muscle atrophy [115].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [115]
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Self-citationAdiponectin and central nervous system disorders: Regulatory mechanisms and therapeutic potential
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Disuse‐induced muscle‐type specific alterations and adiponectin pathway response in male mice
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The role and mechanisms of adipokines in skeletal muscle atrophy
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Self-citation
- Authors
- Singh, A. K., Shree, S., Chattopadhyay, S., Kumar, S., Gurjar, A., Kushwaha, S., Kumar, H., Trivedi, A. K., Chattopadhyay, N., Maurya, R., Ramachandran, R., & Sanyal, S.
- Affiliations
- Central Drug Research Institute (IN)
- Corresponding author
- Sanyal, Sabyasachi
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 439
- Pages
- 273-285
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2519281549
- Cited by
- 42
- References
- 50
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 2 · 2019: 6 · 2018: 2 · 2017: 1 · 2016: 1
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CSIR
- UGC
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- skeletal muscle atrophy, adiponectin receptor agonist, globular adiponectin, AMPK, Akt, PPARγ coactivator-1α, forkhead box O, atrogin-1, MuRF1, dexamethasone-induced atrophy, myogenesis, muscle energetics
- MeSH terms
- Tripartite Motif Proteins, Adenylate Kinase, Animals, Calcium, Cell Differentiation, Cell Line, Dexamethasone, Female, Glucosides, Lipopolysaccharides, Muscle Proteins, Muscular Atrophy, Tumor Necrosis Factor-alpha, Rats, Sprague-Dawley, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Protective Agents, Muscle Development, Myoblasts, Ubiquitin-Protein Ligases, Flavonols, Mice, Adiponectin, Receptors, Adiponectin, Small Molecule Libraries
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