New targets to control skeletal muscle inflammation: MicroRNAs regulated by adiponectin

(eng) Although adipocytes are the main source of circulating adiponectin (ApN), several studies have now shown that ApN may be produced by the skeletal muscle in response to cellular stress. This induction could be a protective mechanism that counteracts inflammation, oxidative stress and cellular damage occurring during skeletal muscle injury. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by inducing target mRNA degradation or blocking translation. In this work, we characterized miRNAs that may contribute to the anti-inflammatory action of ApN on skeletal muscle. To this end, we used ApN-knockout (KO) mice: one tibialis anterior muscle was electroporated with a plasmid coding for the ApN gene while the contralateral leg received a control plasmid. Mice were next challenged by lipopolysaccharide (LPS) to induce inflammation. Muscle electrotransfer of ApN gene induced anti-inflammatory effects: expression of markers of inflammation (TNFα, IL-1β) and oxidative stress (péroxiredonine-3; PRDX3) were downregulated (~−50%) in the muscle electroporated with ApN compared to the contralateral one. miRNA expression profiling revealed that ApN increased the expression of miR-711(~+150%), data which were validated by RT-qPCR. In murine myotubes (C2C12), ApN treatment also upregulated miR-711 and reduced gene expression of TNFα and IL-1β caused by LPS. Transfection of miR-711 mimic reproduced the anti-inflammatory effects of ApN, while using miR-711 inhibitor attenuated these effects. We found that miR-711 repressed 4 genes (fadd, pi3kδ, tab1 and tollip) belonging to the toll-like receptor 4 signalling pathway, which is activated by LPS. In primary cultures of human myotubes, ApN treatment also stimulated the expression of miR-711. The anti-inflammatory effects of ApN appear to be mediated at least in part by miR-711. These data may open new therapeutic perspectives to control muscle inflammation. [Award: Prize of the best poster presentation ]