Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middle-aged rats
Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middle-aged rats
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DOI：
10.14814/phy2.12319
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发表时间：
2015-02-01
影响因子：
2.5
通讯作者：
Edens, Neile K.
中科院分区：
文献类型：
--
作者：
Garvey, Sean M.;Russ, David W.;Edens, Neile K.
我们研究了中年晚期雄性 Sprague Dawley 大鼠（16-17 个月）自愿跑轮活动的分子和代谢组学影响。大鼠被分配连续自愿跑轮进入8周（RW+）或笼匹配但不进入跑轮（RW-）。 9 只 RW+ 大鼠平均每天 83 m（范围：8-163 m），但在 8 周内个体体重增加减少了 84%（4.3 g vs. 26.3 g，P = 0.02），个体平均每日食物摄入量减少了 6.5%（20.6 g vs. 22.0 g，P = 0.09）。禁食过夜后收获后肢肌肉。肌肉重量和肌纤维横截面积显示组间没有差异。使用一组抗体对腓肠肌裂解物进行蛋白质印迹分析表明，跑轮活动改善了氧化代谢（PGC1 α 增加 53%，P = 0.03），增加自噬（LC3B-II/-I 比率增加 36%，P = 0.03），并调节生长信号传导（肌生长抑制素增加 26%，P = 0.04）。 RW+ 肌肉还显示糖原磷酸化酶表达增加了 43%（P = 0.04），糖原含量增加了 45%（P = 0.04）。跖肌和比目鱼肌的代谢组学分析表明，与 RW 大鼠相比，即使是低容量的自愿跑轮活动也与许多长链脂肪酸（例如棕榈油酸、肉豆蔻油酸和二十碳三烯酸）的减少有关。在 RW+ 跖肌中还观察到酰基肉碱和酰基甘油磷脂的相对增加。这些数据表明，即使在中年后期进行少量的体力活动也会促进骨骼肌的广泛代谢重塑。
We examined the molecular and metabolomic effects of voluntary running wheel activity in late middle-aged male Sprague Dawley rats (16-17 months). Rats were assigned either continuous voluntary running wheel access for 8 weeks (RW+) or cage-matched without running wheel access (RW-). The 9 RW+ rats averaged 83 m/day (range: 8-163 m), yet exhibited both 84% reduced individual body weight gain (4.3 g vs. 26.3 g, P = 0.02) and 6.5% reduced individual average daily food intake (20.6 g vs. 22.0 g, P = 0.09) over the 8 weeks. Hindlimb muscles were harvested following an overnight fast. Muscle weights and myofiber cross-sectional area showed no difference between groups. Western blots of gastrocnemius muscle lysates with a panel of antibodies suggest that running wheel activity improved oxidative metabolism (53% increase in PGC1 alpha, P = 0.03), increased autophagy (36% increase in LC3B-II/-I ratio, P = 0.03), and modulated growth signaling (26% increase in myostatin, P = 0.04). RW+ muscle also showed 43% increased glycogen phosphorylase expression (P = 0.04) and 45% increased glycogen content (P = 0.04). Metabolomic profiling of plantaris and soleus muscles indicated that even low-volume voluntary running wheel activity is associated with decreases in many long-chain fatty acids (e.g., palmitoleate, myristoleate, and eicosatrienoate) relative to RW- rats. Relative increases in acylcarnitines and acyl glycerophospholipids were also observed in RW+ plantaris. These data establish that even modest amounts of physical activity during late middle-age promote extensive metabolic remodeling of skeletal muscle.