Endurance Training Attenuates Catabolic Signals Induced by TNF-α in Muscle of Mice

Purpose: To determine whether endurance training attenuates the negative effects induced by an acute injection of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle of mice. Methods: Trained (6 wk of endurance training at 60% of maximal velocity) and untrained mice were injected with TNF-alpha or vehicle and killed 6 h after. Tibialis anterior muscles were analyzed using Western blot and qRT-PCR for markers of inflammation and protein synthesis/degradation. Results: Independently of training, TNF-alpha increased the mRNA of cytokines and downregulated signals linked to protein synthesis. The phosphorylation of IKK alpha/beta and I kappa B alpha induced by TNF-alpha was blunted in trained mice, suggesting altered NF-kappa B activation. This was associated with lower induction of several markers of protein degradation (FoxO1, MURF1, MAFbx, myostatin, Gabarapl1, and LC3BII/LC3BI ratio). Conclusions: Endurance training protects skeletal muscle against the activation of protein degradation signaling pathways induced by TNF-alpha.