Interleukin-6 modifies mRNA expression in mouse skeletal muscle

Aim: The aim of this study was to test the hypothesis that interleukin (IL)-6 plays a role in exercise-induced peroxisome proliferator-activated receptor gamma co-activator (PGC)-1 alpha and tumor necrosis factor (TNF)-alpha mRNA responses in skeletal muscle and to examine the potential IL-6-mediated AMP-activated protein kinase (AMPK) regulation in these responses. Methods: Whole body IL-6 knockout (KO) and wildtype (WT) male mice (4 months of age) performed 1 h treadmill exercise. White gastrocnemius (WG) and quadriceps (Quad) muscles were removed immediately (0') or 4 h after exercise and from mice not run acutely. Results: Acute exercise reduced only in WT muscle glycogen concentration to 55 and 35% (P < 0.05) of resting level in Quad and WG respectively. While AMPK and Acetyl CoA carboxylase (ACC) phosphorylation increased 1.3-fold (P < 0.05) in WG and twofold in Quad immediately after exercise in WT mice, no change was detected in WG in IL-6 KO mice. The PGC-1 alpha mRNA content was in resting WG 1.8-fold higher (P < 0.05) in WT mice than in IL-6 KO mice. Exercise induced a delayed PGC-1 alpha mRNA increase in Quad in IL-6 KO mice (12-fold at 4 h) relative to WT mice (fivefold at 0'). The TNF-alpha mRNA content was in resting Quad twofold higher (P < 0.05) in IL-6 KO than in WT, and WG TNF-alpha mRNA increased twofold (P < 0.05) immediately after exercise only in IL-6 KO. Conclusion: In conclusion, IL-6 affects exercise-induced glycogen use, AMPK signalling and TNF-alpha mRNA responses in mouse skeletal muscle.