Potent anti-inflammatory properties of ApN on the skeletal muscle

Background and aims: Adiponectin (ApN) is an adipokine, which is decreased in the metabolic syndrome, thereby playing a key role in the pathogenesis of these disorders. We have previously shown that ApN exerts important anti-inflammatory effects on skeletal muscle in mice exposed to acute inflammation (LPS injection) or metabolic stress (obesogenic diet). The aim of this work is to test the potency of the anti-inflammatory properties of ApN by using a model with severe and sustained inflammation. Materials and methods: Mdx mice (a mouse model of Duchenne muscular dystrophy, where persistent inflammation worsens the consequences of the genetic deficiency) were crossed with transgenic mice that over express adiponectin (Tg-ApN mice) in order to generate mdx-Tg-ApN mice. Different markers of inflammation/oxidative stress (TNF-α, IL-1β, NF-κB, CD68, CD3, peroxiredoxin 3/5 (PRDX3/5), 4 hydroxynonenal (HNE)) were studied and quantified by immunohistochemistry, ELISA and western blot. In vivo functional tests were also carried out to determine the global force of mice. Finally, the extent of muscle damage was quantified by Evans Blue Dye (EBD) injection following an eccentric exercise. Results: Compared to WT mice, muscles of mdx mice presented significant increases (+ 10 to 15 fold; p<0.001) in the expression of pro-inflammatory factors (TNF-α, IL-1β, NF-κB) and oxidative stress markers (PRDX3/5, HNE) as well as a massive infiltration of macrophages and T lymphocytes as shown by CD68 and CD3 immunolabeling respectively. All of these abnormalities were drastically reduced in mdx-Tg-ApN mice (– 60 to 75 % vs mdx; p<0.001). In addition, mdx-Tg-ApN mice exhibited higher global muscular force (+ 50 % vs mdx; p<0.01) along with a significant decrease in EBD content in their muscle fibers (– 50 to 60 % vs mdx; p<0.001). Conclusion: Adiponectin proves to be an extremely potent anti-inflammatory agent that protects muscle against injury. These anti-inflammatory properties of ApN are of interest in the metabolic syndrome as well as in other diseases where inflammation plays a triggering or worsening pathogenic role