Skeletal muscle atrophy causes decreased physical activity and increased risk of metabolic diseases. We investigated the effects of oleamide (cis-9,10-octadecanamide) treatment on skeletal muscle health. The plasma concentration of endogenous oleamide was approximately 30 nm in male ddY mice under normal physiological conditions. When the stable isotope-labelled oleamide was orally administered to male ddY mice (50 mg/kg), the plasma concentration of exogenous oleamide reached approximately 170 nm after 1 h. Male ddY mice were housed in small cages (one-sixth of normal size) to enforce sedentary behaviour and orally administered oleamide (50 mg/kg per d) for 4 weeks. Housing in small cages decreased tibialis anterior (TA) muscle mass and the cross-sectional area of the myofibres in TA muscle. Dietary oleamide alleviated the decreases in TA muscle and resulted in plasma oleamide concentration of approximately 120 nm in mice housed in small cages. Housing in small cages had no influence on the phosphorylation levels of Akt serine/threonine kinase (Akt), mechanistic target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70S6K) in TA muscle; nevertheless, oleamide increased the phosphorylation levels of the proteins. Housing in small cages increased the expression of microtubule-associated protein 1 light chain 3 (LC3)-II and sequestosome 1 (p62), but not LC3-I, in TA muscle, and oleamide reduced LC3-I, LC3-II and p62 expression levels. In C2C12 myotubes, oleamide increased myotube diameter at ≥100 nm. Furthermore, the mTOR inhibitor, Torin 1, suppressed oleamide-induced increases in myotube diameter and protein synthesis. These results indicate that dietary oleamide rescued TA muscle atrophy in mice housed in small cages, possibly by activating the phosphoinositide 3-kinase/Akt/mTOR signalling pathway and restoring autophagy flux.

中文翻译：

---

油酰胺可挽救小笼子中小鼠的胫骨前肌萎缩

骨骼肌萎缩会导致体力活动减少和代谢疾病风险增加。我们研究了油酰胺的影响（顺式-9,10-octadecanamide) 治疗骨骼肌健康。内源性油酰胺的血浆浓度约为 30 n米在正常生理条件下的雄性 ddY 小鼠中。雄性ddY小鼠口服稳定同位素标记的油酰胺（50 mg/kg）时，外源性油酰胺的血浆浓度达到约170 n米1小时后。将雄性 ddY 小鼠饲养在小笼子中（正常大小的六分之一）以强制久坐行为并口服油酰胺（50 mg/kg/d）4 周。安置在小笼子里减少了胫骨前肌 (TA) 肌肉质量和 TA 肌肉中肌纤维的横截面积。膳食油酰胺减轻了 TA 肌肉的减少，导致血浆油酰胺浓度约为 120 n米关在小笼子里的老鼠。饲养在小笼子里对 TA 肌肉中 Akt 丝氨酸/苏氨酸激酶 (Akt)、雷帕霉素 (mTOR) 和核糖体蛋白 S6 激酶 (p70S6K) 的机械靶点的磷酸化水平没有影响；然而，油酰胺增加了蛋白质的磷酸化水平。饲养在小笼子里增加了 TA 肌肉中微管相关蛋白 1 轻链 3 (LC3)-II 和 sequestosome 1 (p62) 的表达，但不增加 LC3-I，而油酰胺减少了 LC3-I、LC3-II 和 p62表达水平。在 C2C12 肌管中，油酰胺增加肌管直径≥100 n米. 此外，mTOR 抑制剂 Torin 1 抑制了油酰胺诱导的肌管直径和蛋白质合成的增加。这些结果表明，饮食油酰胺挽救了关在小笼子里的小鼠的 TA 肌肉萎缩，可能是通过激活磷酸肌醇 3-激酶/Akt/mTOR 信号通路和恢复自噬通量。