Cited by 34Muscle Physiology and DisordersAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

Skeletal muscle secretome in Duchenne muscular dystrophy: A pivotal anti-inflammatory role of adiponectin

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Lecompte, S., Abou-Samra, M., Boursereau, R., Noel, L., Brichard, S. M.·2017·Cellular and Molecular Life Sciences

Abstract

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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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
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
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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