Oxaloacetate and Ketone Bodies Synergistically Promote Myoblast Differentiation in L6 Cells

Malnutrition and aging are major factors that inhibit myoblast differentiation, leading to a decline in muscle function and contributing to sarcopenia development. This study aimed to elucidate the role of nutrients in myoblast differentiation by establishing a culture system at physiological glucose levels and investigating the effects of ketone bodies and oxaloacetate. We successfully cultured myoblasts at physiological glucose concentrations in a hydrophobic membrane filter-equipped culture flask. Under these conditions, ketone bodies and oxaloacetate synergistically upregulated myogenic differentiation markers (Lmod2 and Ckm), indicating enhanced differentiation. Additionally, oxaloacetate upregulated mitochondrial biogenesis markers (mitochondrial DNA copy number and Cs), whereas ketone bodies promoted Akt phosphorylation, a key regulator of differentiation, via the PI3K/Akt/mTOR pathway. These results suggest that the intake of ketone bodies and oxaloacetate effectively prevents sarcopenia by synergistically promoting myoblast differentiation via distinct molecular mechanisms, suggesting a potential new nutritional strategy.