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bioRxiv · 10.1101/2025.11.02.686003

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

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.
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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--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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/686003v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@e9acddorg.highwire.dtl.DTLVardef@1541b14org.highwire.dtl.DTLVardef@bdfe54org.highwire.dtl.DTLVardef@1844b89_HPS_FORMAT_FIGEXP M_FIG C_FIG

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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.. 2025-11-03. MBOAT2 limits the amounts of PUFA in phosphatidylcholine of neonatal and dystrophic skeletal muscle and promotes muscle regeneration. https://doi.org/10.1101/2025.11.02.686003

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