THE REGULATION OF SKELETAL MUSCLE FUNCTION BY MUSCLE GP130 SIGNALING

Abstract

Chronic inflammation is integral to the pathology of several chronic diseases and has been linked to muscle wasting, weakness, and fatigue resulting in reduced life quality and survival. Interleukin‐6 (IL‐6) signaling through the membrane gp130 receptor has been implicated as a regulator of skeletal muscle mass in both atrophic and hypertrophic conditions through the regulation of STAT3, MAPK, and AKT signaling. Additionally, elevated plasma IL‐6 and associative increases in IL‐6/gp130 signaling have been demonstrated to contribute to disrupted metabolic homeostasis and increased perceived fatigue during chronic disease; however, the regulation of skeletal muscle function by IL‐6/gp130 signaling has not been well described. The purpose of this study was to determine the regulation of skeletal muscle strength and fatigability by gp130 signaling. To test the role of muscle gp130 signaling on muscle strength and fatigability, male gp130 floxed (WT) mice were bred with Cre‐expressing mice driven by myosin light chain to obtain a skeletal muscle specific gp130 knockout (gp130 KO). Both WT and gp130 KO mice were electroporated with an IL‐6 plasmid into the quad to increase circulating IL‐6 for 2 weeks. Littermate controls were electroporated with an empty vector. The functional properties of the Tibialis Anterior (TA) were assessed in situ. Neither gp130 nor elevated plasma IL‐6 (>40pg/mL) had an effect on body or muscle weight. IL‐6 overexpression increased (215%) spleen weight regardless of genotype. While specific force (kN/m2) was reduced (9.8%) in gp130 KO compared to WT, elevated plasma IL‐6 had no effect on TA maximal force across all groups. Muscle fatigability was not different between WT and gp130 KO. Interestingly, elevated plasma IL‐6 increased (15.2%) muscle fatigability in the WT, but had no effect on muscle fatigability in the gp130 KO. Together these results demonstrate that increased levels of IL‐6 accelerates skeletal muscle fatigability through muscle gp130 signaling independent of changes in body weight or skeletal muscle mass.Support or Funding InformationThis work was supported by National Institute of Health (NIH) #NCI‐R01CA121249 (JAC)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.