Activating transcription factor 3 attenuates chemokine and cytokine expression in mouse skeletal muscle after exercise and facilitates molecular adaptation to endurance training

Activating transcription factor (ATF)3 regulates the expression of inflammation-related genes in several tissues under pathological contexts. In skeletalmuscle, atf3 expression increases after exercise, but its target genes remain unknown.We aimed to identify those genes and to determine the influence ofATF3 onmuscle adaptation to training. Skeletalmuscles of ATF3-knockout (ATF3-KO) and controlmice were analyzed at rest, after exercise, and after training. In resting muscles, there was no difference between genotypes in enzymatic activities or fiber type. After exercise, a microarray analysis in quadriceps revealed ATF3 affects genes modulating chemotaxis and chemokine/cytokine activity.Quantitative PCRshowed that themRNAlevels of chemokineC-Cmotif ligand (ccl)8 and chemokine C-X-C motif ligand (cxcl)13 were higher in quadriceps of ATF3-KO mice than in control mice. The same was observed for ccl9 and cxcl13 in soleus. Also in soleus, ccl2, interleukin (il)6, il1b, and cluster of differentiation( cd)68mRNAlevels increasedafter exercise only inATF3-KOmice.Endurance training increasedthebasal mRNA level of hexokinase-2, hormone sensitive lipase, glutathione peroxidase-1, and myosin heavy chain IIa in quadriceps of controlmicebut not inATF3-KOmice. In summary, ATF3 attenuates the expression of inflammationrelated genes after exercise and thus facilitates molecular adaptation to training. - Fernández-Verdejo, R., Vanwynsberghe, A.M., Essaghir, A., Demoulin, J.-B., Hai, T., Deldicque, L., Francaux, M.Activating transcription factor 3 attenuates chemokine and cytokine expression in mouse skeletal muscle after exercise and facilitates molecular adaptation to endurance training.