Onuki Yuji, Nanashima Naoki, Sasaki Yutaro, Kojima-Yuasa Akiko, Norikura Toshio
Graduate School of Health Sciences, Aomori University of Health and Welfare, Aomori 030-8505, Japan.
Graduate School of Human Life and Ecology, Osaka Metropolitan University, Osaka 558-8585, Japan.
Molecules. 2025 May 9;30(10):2101. doi: 10.3390/molecules30102101.
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 ( and ), 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.
营养不良和衰老都是抑制成肌细胞分化的主要因素，会导致肌肉功能下降并促使肌肉减少症的发展。本研究旨在通过建立生理葡萄糖水平的培养系统并研究酮体和草酰乙酸的作用，阐明营养物质在成肌细胞分化中的作用。我们成功地在配备疏水膜过滤器的培养瓶中以生理葡萄糖浓度培养了成肌细胞。在这些条件下，酮体和草酰乙酸协同上调了成肌分化标志物（和），表明分化增强。此外，草酰乙酸上调了线粒体生物合成标志物（线粒体DNA拷贝数和Cs），而酮体则通过PI3K/Akt/mTOR途径促进了Akt磷酸化，Akt是分化的关键调节因子。这些结果表明，摄入酮体和草酰乙酸可通过不同分子机制协同促进成肌细胞分化，从而有效预防肌肉减少症，提示了一种潜在的新营养策略。
