Alkylglycerol enhances myogenesis and regulates ether-phospholipid metabolism in C2C12 myoblasts

1-O-Alkylglycerol (AKG), a lipid characteristic of marine organisms, possesses an ether-linked alkyl chain on its glycerol backbone. AKG exhibits various biological activities, including anti-cancer effects, promoting sperm motility, and stimulating immune response. Metabolically, AKG is converted into alkyl- and alkenyl-phospholipids (PLs), which are key components of the cell membrane and play essential roles in maintaining membrane homeostasis and cellular functions. However, the influence of AKG on myogenesis and ether-type PL metabolism in muscle cells remains unknown. This study evaluated the effects of AKG on myogenic differentiation and ether-PL metabolism in mouse C2C12 myoblasts. During differentiation, cells were treated with 10-20 μM 1-O-octadecyl-glycerol (batyl alcohol) and 1-O-hexadecyl-glycerol (chimyl alcohol). By day 7 of differentiation, myotube size had increased in cells treated with AKGs. Comparative tests using compounds with similar or partial structures, including monoacylglycerol and alkenylglycerol, demonstrated that this activity was linked to the structural features of AKG. Conversely, myotube growth was insufficient after treatment with 1-O-dodecyl-glycerol, which contains a shorter alkyl chain. Additionally, batyl alcohol treatment elevated the levels of ether-phosphatidylcholine (PC) molecular species, including e-PC38:4 and e-PC38:5, those are presumed to bind polyunsaturated fatty acids. Chimyl alcohol treatment also increased ether-PC species, including e-PC36:4 and e-PC36:5 while monoacylglycerol did not alter ether-PC levels. These findings suggest that AKG plays a crucial role in membrane dynamics during myogenesis through metabolic conversion to ether-PLs, providing novel insights into muscle homeostasis to contribute to developing nutritional strategies and preventing and treating muscle diseases.