Chemokine (C‐X‐C motif) ligand 1 is a myokine induced by palmitate and is required for myogenesis in mouse satellite cells

Aim The functional significance of the myokines, cytokines and peptides produced and released by muscle cells has not been fully elucidated. The purpose of this study was to identify a myokine with increased secretion levels in muscle cells due to saturated fatty acids and to examine the role of the identified myokine in the regulation of myogenesis. Methods Human primary myotubes and mouse C2C12 myotubes were used to identify the myokine; its secretion was stimulated by palmitate loading. The role of the identified myokine in the regulation of the activation, proliferation, differentiation and self‐renewal was examined in mouse satellite cells (skeletal muscle stem cells). Results Palmitate loading promoted the secretion of chemokine (C‐X‐C motif) ligand 1 (CXCL1) in human primary myotubes, and it also increased CXCL1 gene expression level in C2C12 myotubes in a dose‐ and time‐dependent manner. Palmitate loading increased the production of reactive oxygen species along with the activation of nuclear factor‐kappa B (NF‐κB) signalling. Pharmacological inhibition of NF‐κB signalling attenuated the increase in CXCL1 gene expression induced by palmitate and hydrogen peroxide. Palmitate loading significantly increased CXC receptor 2 gene expression in undifferentiated cells. CXCL1 knockdown attenuated proliferation and myotube formation by satellite cells, with reduced self‐renewal. CXCL1 knockdown also significantly decreased the Notch intracellular domain protein level. Conclusion These results suggest that secretion of the myokine CXCL1 is stimulated by saturated fatty acids and that CXCL1 promotes myogenesis from satellite cells to maintain skeletal muscle homeostasis.