GABA promotes myoblast fusion and prevents TNF-<i>α</i>-induced muscle protein degradation in C2C12 cells

Gamma-aminobutyric acid (GABA) has been reported to have physiological effects on skeletal muscles, such as maintaining and increasing muscle strength; however, the detailed mechanism is unclear. The aim of this study was to evaluate the effects of GABA on skeletal muscle cells, using C2C12 murine myoblasts as a model of skeletal muscle development. GABA induced elongation of C2C12 myoblasts with F-actin reorganization and then promoted their multinucleation which differentiate myoblasts into multinucleated myotubes through cell fusion. It was also observed that GABA enhances myosin heavy chain (MyHC) protein expression in multinucleated C2C12 cells. Furthermore, tumor necrosis factor-alpha (TNF-α) suppressed MyHC expression in multinucleated C2C12 cells, but GABA avoided its suppressive effect. These results suggest that GABA contributes to the enhancement of muscle protein by supplying myonuclei through cell fusion and eliminates the decline in muscle protein caused by chronic inflammatory cytokines.