title: Involvement of adiponectin in the pathogenesis of dystrophinopathy.
abstract: BACKGROUND
  The hormone adiponectin (ApN) is decreased in the metabolic syndrome, where it plays a key pathogenic role. ApN also exerts some anti-inflammatory effects on skeletal muscles in mice exposed to acute or chronic inflammation. Here, we investigate whether ApN could be sufficiently potent to counteract a severe degenerative muscle disease, with an inflammatory component such as Duchenne muscular dystrophy (DMD).
  
  
  METHODS
  Mdx mice (a DMD model caused by dystrophin mutation) were crossed with mice overexpressing ApN in order to generate mdx-ApN mice; only littermates were used. Different markers of inflammation/oxidative stress and components of signaling pathways were studied. Global force was assessed by in vivo functional tests, and muscle injury with Evans Blue Dye (EBD). Eventually, primary cultures of human myotubes were used.
  
  
  RESULTS
  Circulating ApN was markedly diminished in mdx mice. Replenishment of ApN strikingly reduced muscle inflammation, oxidative stress, and enhanced the expression of myogenic differentiation markers along with that of utrophin A (a dystrophin analog) in mdx-ApN mice. Accordingly, mdx-ApN mice exhibited higher global force and endurance as well as decreased muscle damage as quantified by curtailed extravasation of EBD in myofibers. These beneficial effects of ApN were recapitulated in human myotubes. ApN mediates its protection via the adiponectin receptor 1 (AdipoR1, the main ApN receptor in muscle) and the AMPK-SIRT1-PGC-1α signaling pathway, leading to downregulation of the nuclear factor kappa B (NF-κB) and inflammatory genes, together with upregulation of utrophin.
  
  
  CONCLUSIONS
  Adiponectin proves to be an extremely powerful hormone capable of protecting the skeletal muscle against inflammation and injury, thereby offering novel therapeutic perspectives for dystrophinopathies.
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Abou-Samra
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lecompte
authors.affiliation: Cellular and Molecular Unit, Institute of Neuroscience, Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Schakman
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Noel
authors.affiliation: Experimental Morphology Unit, Institute of Experimental and Clinical Research, Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Many
authors.affiliation: Cellular and Molecular Unit, Institute of Neuroscience, Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gailly
authors.affiliation: Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector, Catholic University of Louvain, 1200 Brussels, Belgium.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Brichard
keywords: AMPK signaling; Adiponectin; Inflammation; Mdx; NF-κB; Skeletal muscle; Utrophin