Skeletal muscle secretome in Duchenne muscular dystrophy: A pivotal anti-inflammatory role of adiponectin
Open accessAbstract
BACKGROUND: Persistent inflammation exacerbates the progression of Duchenne muscular dystrophy (DMD). The hormone, adiponectin (ApN), which is decreased in the metabolic syndrome, exhibits anti-inflammatory properties on skeletal muscle and alleviates the dystrophic phenotype of mdx mice. Here, we investigate whether ApN retains its anti-inflammatory action in myotubes obtained from DMD patients. We unravel the underlying mechanisms by studying the secretome and the early events of ApN. METHODS: Primary cultures of myotubes from DMD and control patients were treated or not by ApN after an inflammatory challenge. Myokines secreted in medium were identified by cytokine antibody-arrays and ELISAs. The early events of ApN signaling were assessed by abrogating selected genes. RESULTS: ApN retained its anti-inflammatory properties in both dystrophic and control myotubes. Profiling of secretory products revealed that ApN downregulated the secretion of two pro-inflammatory factors (TNFα and IL-17A), one soluble receptor (sTNFRII), and one chemokine (CCL28) in DMD myotubes, while upregulating IL-6 that exerts some anti-inflammatory effects. These changes were explained by pretranslational mechanisms. Earlier events of the ApN cascade involved AdipoR1, the main receptor for muscle, and the AMPK-SIRT1-PGC-1α axis leading, besides alteration of the myokine profile, to the upregulation of utrophin A (a dystrophin analog). CONCLUSION: ApN retains its beneficial properties in dystrophic muscles by activating the AdipoR1-AMPK-SIRT1-PGC-1α pathway, thereby inducing a shift in the secretion of downstream myokines toward a less inflammatory profile while upregulating utrophin. ApN, the early events of the cascade and downstream myokines may be therapeutic targets for the management of DMD.
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ApN disclosed strong anti-inflammatory properties in human myotubes when submitted to an inflammatory challenge.
“Moreover, ApN disclosed strong anti-inflammatory properties in human myotubes when submitted to an inflammatory challenge [56,57].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [57]
The anti-inflammatory effects of ApN in human healthy myotubes were linked to activation of the AdipoR1-AMPK-SIRT1-PGC-1α pathway.
“Mechanistically, the anti-inflammatory effects of ApN in human “healthy” myotubes were linked to activation of the AdipoR1-AMPK-SIRT1-PGC-1α pathway [56,57].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [57]
Myotubes from DMD patients were unable to produce ApN for local protection, unlike non-dystrophic myotubes challenged by inflammation.
“Moreover, myotubes from DMD patients were unable to produce ApN for local protection [57], unlike non-dystrophic myotubes challenged by inflammation [36].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [57]
Secretome analysis from myotubes revealed that ApN down-regulated the secretion of TNFα, IL-17A, sTNFRII, and CCL28.
“secretome analysis from myotubes revealed that ApN down-regulated the secretion of two pro-inflammatory factors (TNFα and IL-17A), one soluble receptor (sTNFRII), and one chemokine (CCL28) [57].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [57]
ApN/AdipoRon supplementation induced a shift in the secretion of downstream myokines toward a less inflammatory profile in DMD human myotubes.
“and induced a shift in the secretion of downstream myokines toward a less inflammatory profile.”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [57]
The mechanisms leading to protective effects of ApN/AdipoRon in DMD involved activation of the AdipoR1-AMPK-SIRT1-PGC-1α axis both in vivo (mdx mice) and in vitro (human dystrophic myotubes).
“As in healthy muscle, the mechanisms leading to the protective effects of ApN/AdipoRon in DMD involved the activation of the AdipoR1-AMPK-SIRT1-PGC-1α axis both in vivo (mdx mice) or in vitro (human dystrophic myotubes) [56,57,103]”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [57]
ApN/AdipoRon supplementation retained its anti-inflammatory properties in DMD human myotubes.
“We found that ApN/AdipoRon supplementation retained its anti-inflammatory properties in DMD human myotubes [56,57,103]”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [57]
Silencing each component of the AdipoR1-AMPK-SIRT1-PGC-1α cascade abrogated the effects of ApN/AdipoRon.
“Silencing each component of this cascade abrogated the effects of ApN/AdipoRon.”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [57]
Up-regulation of utrophin partly substitutes for dystrophin deficiency.
“Third, up-regulation of utrophin partly substitutes for dystrophin deficiency [56,57].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [57]
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Adiponectin—Consideration for its Role in Skeletal Muscle Health
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Self-citation<scp>AdipoRon</scp>, a new therapeutic prospect for Duchenne muscular dystrophy
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- Authors
- Lecompte, S., Abou-Samra, M., Boursereau, R., Noel, L., & Brichard, S. M.
- Affiliations
- UCLouvain (BE)
- Corresponding author
- Brichard, S. M.
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2017-02-10
- Volume
- 74
- Issue
- 13
- Pages
- 2487-2501
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC5487898
- OpenAlex
- W2586135403
- Cited by
- 34
- References
- 51
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 1
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cellular and Molecular Life Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- Funders
- Foundation of Scientific and Medical Research (1.5097.12, T.0212.13)
- General Division of Scientific Research (ARC 12 -17/047)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- Duchenne muscular dystrophy, adiponectin, myokines, muscle inflammation, AdipoR1, TNF-α, IL-17A, CCL28, interleukin-6, myotubes
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adolescent, Adult, Anti-Inflammatory Agents, Child, Female, Gene Expression Regulation, Humans, Inflammation, Male, RNA, Messenger, Biomarkers, Muscle, Skeletal, Muscle Fibers, Skeletal, Muscular Dystrophy, Duchenne, Proteome, RNA, Small Interfering, Utrophin, Adiponectin, Receptors, Adiponectin, Young Adult, Sirtuin 1
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