Involvement of adiponectin in the pathogenesis of dystrophinopathies

The hormone adiponectin (ApN) is decreased in the metabolic syndrome, where it plays a key pathogenic role. We have previously shown that ApN exerts anti-inflammatory effects on the skeletal muscle in mice exposed to acute inflammation (lipopolysaccharide injection) or metabolic stress (obesogenic diet). Here we investigate whether ApN could be sufficiently potent to counteract a severe degenerative muscular disease. To this end, mdx mice (a model of Duchenne muscular dystrophy, where inflammation worsens the consequences of the genetic deficiency) were crossed with transgenic mice overexpressing ApN in order to generate mdx-ApN mice. Circulating ApN was markedly reduced in mdx mice compared to controls. Replenishment of ApN drastically reduced inflammation and oxidative stress in muscles of mdx-ApN mice and enhanced the expression of myogenic differentiation markers. Moreover, mdx-ApN mice exhibited higher global muscle force and endurance along with decreased muscle damage as quantified by curtailed extravasation of Evans Blue Dye in myofibers. Lastly, the anti-inflammatory effects of ApN were also reproduced in human myotubes in vitro. Adiponectin turns out to be an extremely potent anti-inflammatory hormone that protects the skeletal muscle against injury. These properties of ApN may be of interest in myopathies, but also in several other diseases where inflammation plays a triggering or worsening pathogenic role [Award: Prize of the best oral presentation