title: Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Catholic University of Louvain, UCL/EDIN B1.55.06 - Av. Hippocrate, 55B-1200, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Lecompte
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Catholic University of Louvain, UCL/EDIN B1.55.06 - Av. Hippocrate, 55B-1200, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Abou-Samra
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Catholic University of Louvain, UCL/EDIN B1.55.06 - Av. Hippocrate, 55B-1200, Brussels, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Boursereau
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Catholic University of Louvain, UCL/EDIN B1.55.06 - Av. Hippocrate, 55B-1200, Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Noel
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Catholic University of Louvain, UCL/EDIN B1.55.06 - Av. Hippocrate, 55B-1200, Brussels, Belgium. Sonia.Brichard@uclouvain.be.
authors.forename: S M
authors.initials: SM
authors.lastname: Brichard
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D049411:Utrophin / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020543:Proteome; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D049411:Utrophin; D056564:Sirtuin 1
keywords: ApN; DMD; Human myotubes; Inflammation; Muscle secretion