Potential therapeutic action of AdipoRon in Duchenne Muscular Dystrophy

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, through AdipoR1 (ApN muscle receptor) and AMPK pathway. These effects have been studied in the context of Duchenne muscular dystrophy (DMD), a disease caused by dystrophin deficiency and characterized by a progressive muscle weakness/necrosis together with a significant inflammatory component. In mdx mice, a murine model of the disease, ApN had powerful protective effects against muscle inflammation, oxidative stress and significantly improved physical performance as well as myogenesis. Therefore, ApN constitutes a new interesting therapeutic agent for the management of DMD. Recently, an orally active ApN receptor agonist, AdipoRon, has been identified. This synthetic small molecule has the advantage of being more easily produced and administrated than ApN. The aim of this work was to determine if AdipoRon has similar effects to those of ApN on the dystrophic muscle. To achieve this, we treated mdx mice daily with AdipoRon for 8 weeks. Results demonstrated that this treatment improved the physical performance of the mdx mouse and prevented the progression of the dystrophic pathology by counteracting excessive inflammation and oxidative reactions. AdipoRon also improved muscle regeneration and promoted a muscle fiber shift towards a more oxidative phenotype protecting thus the muscle membrane from mechanical damage. The anti-inflammatory properties of AdipoRon were also recapitulated in vitro in human myotubes. These results demonstrate that AdipoRon exerts beneficial effects similar to those of ApN on the dystrophic muscle, thus making it a promising therapeutic prospect for the treatment of DMD and other muscular diseases where inflammation plays an important role