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Article

Oxaloacetate and Ketone Bodies Synergistically Promote Myoblast Differentiation in L6 Cells

by
Yuji Onuki
1,
Naoki Nanashima
1,
Yutaro Sasaki
1,2,
Akiko Kojima-Yuasa
2 and
Toshio Norikura
1,*
1
Graduate School of Health Sciences, Aomori University of Health and Welfare, Aomori 030-8505, Japan
2
Graduate School of Human Life and Ecology, Osaka Metropolitan University, Osaka 558-8585, Japan
*
Author to whom correspondence should be addressed.
Molecules 2025, 30(10), 2101; https://doi.org/10.3390/molecules30102101
Submission received: 27 February 2025 / Revised: 16 April 2025 / Accepted: 7 May 2025 / Published: 9 May 2025
(This article belongs to the Special Issue Functional Foods and Dietary Bioactives in Human Health)
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Abstract

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.
Keywords: myoblast; myotube; differentiation; myogenesis; ketone bodies; oxaloacetate myoblast; myotube; differentiation; myogenesis; ketone bodies; oxaloacetate
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MDPI and ACS Style

Onuki, Y.; Nanashima, N.; Sasaki, Y.; Kojima-Yuasa, A.; Norikura, T. Oxaloacetate and Ketone Bodies Synergistically Promote Myoblast Differentiation in L6 Cells. Molecules 2025, 30, 2101. https://doi.org/10.3390/molecules30102101

AMA Style

Onuki Y, Nanashima N, Sasaki Y, Kojima-Yuasa A, Norikura T. Oxaloacetate and Ketone Bodies Synergistically Promote Myoblast Differentiation in L6 Cells. Molecules. 2025; 30(10):2101. https://doi.org/10.3390/molecules30102101

Chicago/Turabian Style

Onuki, Yuji, Naoki Nanashima, Yutaro Sasaki, Akiko Kojima-Yuasa, and Toshio Norikura. 2025. "Oxaloacetate and Ketone Bodies Synergistically Promote Myoblast Differentiation in L6 Cells" Molecules 30, no. 10: 2101. https://doi.org/10.3390/molecules30102101

APA Style

Onuki, Y., Nanashima, N., Sasaki, Y., Kojima-Yuasa, A., & Norikura, T. (2025). Oxaloacetate and Ketone Bodies Synergistically Promote Myoblast Differentiation in L6 Cells. Molecules, 30(10), 2101. https://doi.org/10.3390/molecules30102101

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