Folic acid is a water-soluble
vitamin in the B-complex group, and an exogenous intake is required for health, growth and development. As a precursor to co-factors,
folic acid is required for one-
carbon donors in the synthesis of
DNA bases and other essential biomolecules. A lack of dietary
folic acid can lead to
folic acid deficiency and can therefore result in several health problems, including
macrocytic anemia, elevated plasma
homocysteine levels,
cardiovascular disease,
birth defects,
carcinogenesis,
muscle weakness and difficulty in walking. Previous studies have indicated that
folic acid exerts a positive effect on skeletal muscle functions. However, the precise role of
folic acid in skeletal muscle cell differentiation remains poorly understood. Thus, in the present study, we examined the effects of
folic acid on neo-myotube maturation and differentiation using C2C12 murine myoblasts. We found that
folic acid promoted the formation of multinucleated myotubes, and increased the fusion index and
creatine kinase (CK) activity in a concentration-dependent manner. In addition, western blot analysis revealed that the expression levels of the muscle-specific marker,
myosin heavy chain (MyHC), as well as those of the myogenic regulatory factors (MRFs), MyoD and
myogenin, were increased in the
folic acid-treated myotubes during myogenic differentiation.
Folic acid also promoted the activation of the Akt pathway, and this effect was inhibited by treatment of the C2C12 cells with
LY294002 (Akt inhibitor). Blocking of the Akt pathway with a specific inhibitor revealed that it was necessary for mediating the stimulatory effects of
folic acid on muscle cell differentiation and fusion. Taken together, our data suggest that
folic acid promotes the differentiation of C2C12 cells through the activation of the Akt pathway.