Potential therapeutic action of adiponectin in Duchenne muscular dystrophy
(2016) 21st International Congress of the World Muscle Society — Location: (Spain) Granada (4.October.2016)
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- Adiponectin (ApN) is a hormone tightly linked to the metabolic syndrome where it exerts anti-diabetic actions. It is also known to possess powerful anti-inflammatory effects on skeletal muscle exposed to acute and chronic inflammation. We have previously tested the implication of ApN in Duchenne Muscular Dystrophy (DMD) by generating transgenic mdx mice overexpressing ApN. We showed that ApN can act as preventive agent and delay disease progression. ApN upregulation was capable of reducing muscle inflammation/injury and improving force/myogenesis. Here we took an a contrario approach and crossed mdx mice with ApN knockout mice, in order to obtain mdx with ApN depletion (mdx-KO). The aims were to (1) test whether ApN deficiency could worsen the mdx phenotype and (2) test if ApN supplementation can counteract all abnormalities once the disease has settled. Mdx-KO mice exhibited lower global muscle force/endurance as well as increased muscle damage when compared to regular mdx mice. We next injected and electro-transferred one tibialis anterior with the ApN gene, while the contralateral muscle received and empty plasmid and served as a control. Local administration of the ApN gene significantly reduced the expression of two oxidative stress markers (PRDX3, HNE), two inflammatory markers (TNFα, IL-1β), as well as the number of M1 macrophages. In addition, the expression of an anti-inflammatory cytokine (IL-10) was markedly increased. Local administration of ApN was also able to increase the expression of two major factors of muscle differentiation (Myogenin, Mrf4), one key marker of muscle regeneration (Myh3), plus induce a switch towards a resistant oxidative fiber phenotype. Finally, the presence of ApN markedly reduced NF-κB, a maestro of muscle inflammation and myogenesis. ApN proves to be, yet again, a powerful protector of the skeletal muscle, thus making it a potential therapeutic agent for DMD, and for other diseases where inflammation plays a crucial role. [Award: the Duchenne research fund prize, for the best presentation by a young researcher on the treatment of Duchenne muscular dystrophy]
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Abou Samra, M., Boursereau, R., Noel, L., & Brichard, S. (2016). Potential therapeutic action of adiponectin in Duchenne muscular dystrophy. Neuromuscular Disorders, 26, S129. https://doi.org/10.1016/j.nmd.2016.06.159 (Original work published 2016)