Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
Laboratory of Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
J Biol Chem. 2023 Jul;299(7):104848. doi: 10.1016/j.jbc.2023.104848. Epub 2023 May 20.
Skeletal muscle consists of both fast- and slow-twitch fibers. Phospholipids are important structural components of cellular membranes, and the diversity of their fatty acid composition affects membrane characteristics. Although some studies have shown that acyl chain species in phospholipids differ among various muscle fiber types, the mechanisms underlying these differences are unclear. To investigate this, we analyzed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecules in the murine extensor digitorum longus (EDL; fast-twitch) and soleus (slow-twitch) muscles. In the EDL muscle, the vast majority (93.6%) of PC molecules was palmitate-containing PC (16:0-PC), whereas in the soleus muscle, in addition to 16:0-PC, 27.9% of PC molecules was stearate-containing PC (18:0-PC). Most palmitate and stearate were bound at the sn-1 position of 16:0- and 18:0-PC, respectively, and 18:0-PC was found in type I and IIa fibers. The amount of 18:0-PE was higher in the soleus than in the EDL muscle. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) increased the amount of 18:0-PC in the EDL. Lysophosphatidylglycerol acyltransferase 1 (LPGAT1) was highly expressed in the soleus compared with that in the EDL muscle and was upregulated by PGC-1α. LPGAT1 knockout decreased the incorporation of stearate into PC and PE in vitro and ex vivo and the amount of 18:0-PC and 18:0-PE in murine skeletal muscle with an increase in the level of 16:0-PC and 16:0-PE. Moreover, knocking out LPGAT1 decreased the amount of stearate-containing phosphatidylserine (18:0-PS), suggesting that LPGAT1 regulated the acyl chain profiles of phospholipids, namely, PC, PE, and PS, in the skeletal muscle.
骨骼肌由快肌纤维和慢肌纤维组成。磷脂是细胞膜的重要结构成分，其脂肪酸组成的多样性会影响膜的特性。虽然一些研究表明，不同肌肉纤维类型的磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）中的酰基链种类不同，但这些差异的机制尚不清楚。为了研究这一点，我们分析了小鼠伸趾长肌（EDL；快肌）和比目鱼肌（慢肌）中的 PC 和 PE 分子。在 EDL 肌肉中，绝大多数（93.6%）的 PC 分子是含有棕榈酸的 PC（16:0-PC），而在比目鱼肌中，除了 16:0-PC 外，27.9%的 PC 分子是含有硬脂酸的 PC（18:0-PC）。大多数棕榈酸和硬脂酸分别位于 16:0-和 18:0-PC 的 sn-1 位置，18:0-PC 存在于 I 型和 IIa 型纤维中。比目鱼肌中的 18:0-PE 含量高于 EDL 肌肉。过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）增加了 EDL 中 18:0-PC 的含量。与 EDL 肌肉相比，LPGAT1 在比目鱼肌中的表达水平较高，并且受 PGC-1α 上调。LPGAT1 敲除减少了棕榈酸在 PC 和 PE 中的掺入以及体外和体内的 18:0-PC 和 18:0-PE 的含量，并增加了 16:0-PC 和 16:0-PE 的水平。此外，敲除 LPGAT1 减少了含有硬脂酸的磷脂酰丝氨酸（18:0-PS）的含量，这表明 LPGAT1 调节了骨骼肌中 PC、PE 和 PS 等磷脂的酰基链谱。
