The effect of phospholipid remodeling by LPGAT1 on muscle characterization and function

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K21224
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0909:Sports sciences, physical education, health sciences, and related fields
• Research Institution: University of Shizuoka
• Principal Investigator: Satp Tomoki 静岡県立大学, 食品栄養科学部, 助教 (30908455)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: リン脂質 / リポクオリティ / 骨格筋 / 筋萎縮 / 筋機能

Outline of Final Research Achievements

In this study, we focused on the lipo-quality of glycerophospholipids in skeletal muscle, especially phosphatidylcholine (PC) bound with stearic acid (18:0). We found that muscle atrophy occurs in fast-twitch muscle fibers of genetically modified mice with excessively increased amounts of 18:0-PC. Type 2b fibers, fast-twitch fibers, showed a reduction in the cross-sectional area of the muscle. In addition, the mice had more myofibers containing the central nucleus, observed during regeneration, and changes in protein expression observed during muscle injury. These results suggest that skeletal muscle lipo-quality contributes to the properties of skeletal muscle. A decrease in limb grip strength was also observed, suggesting that changes in muscle properties via changes in muscle lipo-quality affect muscle function.

Free Research Field

栄養学

Academic Significance and Societal Importance of the Research Achievements

近年、リポクオリティの違いが臓器機能に及ぼす影響が明らかになりつつあるが骨格筋機能との関係性は不明瞭であった。本研究では遅筋線維に多く含まれる18:0-PCに着目して、遺伝子組み換えによって18:0-PCが過剰になるモデルを作製し、筋性状・機能に及ぼす影響を検証した。その結果、大きな表現型として速筋線維における筋萎縮を発見した。細胞を構成する脂質分子の変化が筋萎縮に影響することはこれまでに報告がなく、新たな筋萎縮予防の標的となり得る。今後さらに細胞のどこで(オルガネラなど)脂質が変化しているかを明確にすることで、新たな筋萎縮発症機序の発見に結び付くことが期待される。