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MBOAT2 limits the amounts of PUFA in phosphatidylcholine of neonatal and dystrophic skeletal muscle and promotes muscle regeneration

Created on 05 Nov 2025

Authors

Valentine, W. J., Tokuoka, S. M., Hashidate-Yoshida, T., Yanagida, K., Suzuki, T., Inagaki, N. F., Motohashi, N., Nakano, K., Okamura, T., Kita, Y., Shindou, H., Aoki, Y., Shimizu, T.

Abstract

Skeletal muscle regeneration is critically shaped by lipid remodeling, yet regulatory mechanisms involved remain unexplored. We identify MBOAT2, a lysophospholipid acyltransferase highly induced in activated satellite cells, as a key enzyme that limits the amounts of polyunsaturated fatty acids (PUFAs) in phosphatidylcholine (PC). Lipidomic profiling reveals a characteristic PC signature which is high in monounsaturated fatty acids (MUFAs) and low in PUFAs in dystrophic, injured, and neonatal muscle, paralleling elevated Mboat2 expression. Given the susceptibility of PUFAs to oxidative damage and the emerging role of lipid peroxidation in driving muscle atrophy during denervation, disuse, and aging, MBOAT2-mediated enrichment of MUFA-PC may represent a protective and pro-regenerative lipid environment. Loss- and gain-of-function approaches confirm that MBOAT2 remodels PC and promotes myogenic repair. Our findings uncover a lipid remodeling circuit in muscle stem cells that buffers oxidative stress and highlight that MBOAT2 may improve regenerative capacity in muscular dystrophy, sarcopenia, and other muscle-wasting conditions.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 05 Nov 2025.

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