Obesity alters skeletal muscle lipidome and promotes myopathy, but it is unknown whether aberrant muscle lipidome contributes to the reduction in skeletal muscle contractile force-generating capacity. Comprehensive lipidomic analyses of mouse skeletal muscle revealed a very strong positive correlation between the abundance of lysophosphatidylcholine (lyso-PC), a class of lipids that is known to be downregulated with obesity, with maximal tetanic force production. The level of lyso-PC is regulated primarily by lyso-PC acyltransferase 3 (LPCAT3), which acylates lyso-PC to form phosphatidylcholine. Tamoxifen-inducible skeletal muscle-specific overexpression of LPCAT3 (LPCAT3-MKI) was sufficient to reduce muscle lyso-PC content in both standard chow diet- and high-fat diet (HFD)-fed conditions. Strikingly, the assessment of skeletal muscle force-generating capacity ex vivo revealed that muscles from LPCAT3-MKI mice were weaker regardless of diet. Defects in force production were more apparent in HFD-fed condition, where tetanic force production was 40% lower in muscles from LPCAT3-MKI compared to that of control mice. These observations were partly explained by reductions in the cross-sectional area in type IIa and IIx fibers, and signs of muscle edema in the absence of fibrosis. Future studies will pursue the mechanism by which LPCAT3 may alter protein turnover to promote myopathy.

中文翻译：

---

低溶血磷脂酰胆碱诱发骨骼肌肌病，高脂饮食喂养加重

肥胖会改变骨骼肌脂质组并促进肌病，但尚不清楚异常的肌肉脂质组是否会导致骨骼肌产生收缩力的能力下降。小鼠骨骼肌的综合脂质组学分析表明，溶血磷脂酰胆碱 (lyso-PC) 的丰度与最大强直力产生之间存在非常强的正相关关系，溶血磷脂酰胆碱 (lyso-PC) 是一类已知会因肥胖而下调的脂质。lyso-PC 的水平主要受 lyso-PC 酰基转移酶 3 (LPCAT3) 调节，该酶使 lyso-PC 酰化形成磷脂酰胆碱。他莫昔芬诱导的 LPCAT3 骨骼肌特异性过表达 (LPCAT3-MKI) 足以降低标准食物和高脂饮食 (HFD) 喂养条件下的肌肉溶血 PC 含量。引人注目的是，离体骨骼肌力产生能力的评估表明，无论饮食如何，LPCAT3-MKI 小鼠的肌肉都较弱。力产生的缺陷在 HFD 喂养条件下更为明显，与对照小鼠相比，LPCAT3-MKI 肌肉的强直力产生低 40%。这些观察结果的部分原因是 IIa 型和 IIx 型纤维的横截面积减少，以及在没有纤维化的情况下出现肌肉水肿迹象。未来的研究将探索 LPCAT3 可能改变蛋白质周转以促进肌病的机制。这些观察结果的部分原因是 IIa 型和 IIx 型纤维的横截面积减少，以及在没有纤维化的情况下出现肌肉水肿迹象。未来的研究将探索 LPCAT3 可能改变蛋白质周转以促进肌病的机制。这些观察结果的部分原因是 IIa 型和 IIx 型纤维的横截面积减少，以及在没有纤维化的情况下出现肌肉水肿迹象。未来的研究将探索 LPCAT3 可能改变蛋白质周转以促进肌病的机制。