Fasting rapidly (≤ 6 h) activates mitochondrial biogenic pathways in rodent muscle, an effect that is absent in human muscle following prolonged (10–72 h) fasting. We tested the hypotheses that fasting-induced changes in human muscle occur shortly after food withdrawal and are modulated by whole-body energetic stress. Vastus lateralis biopsies were obtained from ten healthy males before, during (4 h), and after (8 h) two supervised fasts performed with (FAST+EX) or without (FAST) 2 h of arm ergometer exercise (~ 400 kcal of added energy expenditure). PGC-1α mRNA (primary outcome measure) was non-significantly reduced (p = 0.065 [η_p² = 0.14]) whereas PGC-1α protein decreased (main effect of time: p < 0.01) during both FAST and FAST+EX. P53 acetylation increased in both conditions (main effect of time: p < 0.01) whereas ACC and SIRT1 phosphorylation were non-significantly decreased (both p < 0.06 [η_p² = 0.15]). Fasting-induced increases in NFE2L2 and NRF1 protein were observed (main effects of time: p < 0.03), though TFAM and COXIV protein remained unchanged (p > 0.05). Elevating whole-body energetic stress blunted the increase in p53 mRNA, which was apparent during FAST only (condition × time interaction: p = 0.04). Select autophagy/mitophagy regulators (LC3BI, LC3BII, BNIP3) were non-significantly reduced at the protein level (p ≤ 0.09 [η_p² > 0.13]) but the LC3II:I ratio was unchanged (p > 0.05). PDK4 mRNA (p < 0.01) and intramuscular triglyceride content in type IIA fibers (p = 0.04) increased similarly during both conditions. Taken together, human skeletal muscle signaling, mRNA/protein expression, and substrate storage appear to be unaffected by whole-body energetic stress during the initial hours of fasting.

快速禁食（≤ 6 小时）会激活啮齿动物肌肉中的线粒体生物源通路，这种效应在长期禁食（10-72 小时）后在人类肌肉中不存在。我们测试了禁食引起的人类肌肉变化在食物戒断后不久发生并受全身能量压力调节的假设。股外侧肌活检取自 10 名健康男性之前、期间 (4 小时) 和之后 (8 小时) 进行的两次有监督的禁食 (FAST + EX) 或不 (FAST) 2 小时手臂测力计运动（添加约 400 kcal能量消耗）。PGC-1α mRNA（主要结果测量）未显着降低（p  = 0.065 [η _p ²  = 0.14]），而 PGC-1α 蛋白降低（时间的主要影响：p < 0.01) 在 FAST 和 FAST+EX 期间。P53 乙酰化在两种条件下均增加（时间的主要影响：p  < 0.01），而 ACC 和 SIRT1 磷酸化未显着降低（均p  < 0.06 [η _p ²  = 0.15]）。观察到禁食诱导的 NFE2L2 和 NRF1 蛋白增加（时间的主要影响：p  < 0.03），尽管 TFAM 和 COXIV 蛋白保持不变（p  > 0.05）。提高全身能量压力减弱了p53 mRNA的增加，这仅在 FAST 期间很明显（条件 × 时间相互作用：p  = 0.04）。选择的自噬/线粒体自噬调节因子（LC3BI、LC3BII、BNIP3）在蛋白质水平上没有显着降低（p  ≤ 0.09 [η _p ²  > 0.13])，但 LC3II:I 比率没有变化 ( p  > 0.05)。 在两种情况下， IIA 型纤维中的PDK4 mRNA ( p < 0.01) 和肌内甘油三酯含量 ( p = 0.04) 的增加相似。总之，人类骨骼肌信号、mRNA/蛋白质表达和底物储存在禁食的最初几个小时似乎不受全身能量压力的影响。