Adiponectin, a powerful brake on skeletal muscle inflammation and injury
(2015) 20th International Congress of The World Muscle Society — Location: (United Kingdom) Brighton (1.October.2015)
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- The hormone adiponectin (ApN) is decreased in metabolic syndrome, where it plays a key pathogenic role. ApN exerts anti-inflammatory effects on skeletal muscles in mice exposed to acute (lipopolysaccharide injection) or chronic inflammation (obesogenic diet). Here we investigated whether ApN could be sufficiently potent to counteract a severe degenerative muscle disease. To this end, mdx mice (a model of Duchenne muscular dystrophy, where dystrophin is absent and a severe inflammation worsens the disease) were crossed with transgenic mice overexpressing ApN in order to generate mdx–ApN mice. 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 in mdx–ApN mice. 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. These beneficial effects of ApN were also recapitulated in human myotubes in vitro. ApN seems to mediate its protective effects via the AdipoR1 (ApN main muscle receptor) and AMPK-SIRT1-PGC-1α signalling pathway, which leads to a downregulation of NF-κB activity and the expression of inflammatory genes along with an upregulation of utrophin in muscle fibers. Utrophin, an endogenous homolog of dystrophin, will thus help rescue the dystrophic phenotype. Adiponectin proves to be an extremely powerful hormone capable of protecting the skeletal muscle against inflammation and injury, thereby offering new therapeutic interests for dystrophinopathies.
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Abou Samra, M., Lecompte, S., Schakman, O., Noel, L., Lafosse, A., Many, M.-C., Gailly, P., & Brichard, S. (2015). Adiponectin, a powerful brake on skeletal muscle inflammation and injury. Neuromuscular Disorders, 25, S292. https://doi.org/10.1016/j.nmd.2015.06.379 (Original work published 2015)