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 (<i>Lmod2</i> and <i>Ckm</i>), 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.