School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
Pflugers Arch. 2021 Feb;473(2):241-252. doi: 10.1007/s00424-020-02499-7. Epub 2021 Jan 8.
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 = 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 = 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 > 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发生途径，而在长时间（10-72 小时）禁食后，这种作用在人类肌肉中不存在。我们检验了以下假设：禁食引起的人类肌肉变化在禁食后不久就会发生，并且会受到全身能量应激的调节。在两次监督禁食中，从 10 名健康男性的股外侧肌中获取活检样本，禁食前（基础）、禁食中（4 小时）和禁食后（8 小时）。两次禁食分别为（FAST+EX）和（FAST），其中 FAST+EX 组还进行了 2 小时的手臂测力计运动（约 400 千卡的额外能量消耗）。PGC-1αmRNA（主要观察指标）虽无显著降低（p=0.065[η=0.14]），但在 FAST 和 FAST+EX 期间均降低（时间主效应：p<0.01）。P53 乙酰化在两种情况下均增加（时间主效应：p<0.01），而 ACC 和 SIRT1 磷酸化则无显著降低（均 p<0.06[η=0.15]）。观察到禁食诱导的 NFE2L2 和 NRF1 蛋白增加（时间主效应：p<0.03），尽管 TFAM 和 COXIV 蛋白保持不变（p>0.05）。全身能量应激增加会使 p53mRNA 增加，而这种增加仅在 FAST 期间出现（条件×时间交互作用：p=0.04）。一些自噬/线粒体自噬调节剂（LC3BI、LC3BII、BNIP3）在蛋白质水平上无显著降低（p≤0.09[η>0.13]），但 LC3II:I 比值不变（p>0.05）。PDK4mRNA（p<0.01）和 IIA 型纤维内的肌内甘油三酯含量（p=0.04）在两种情况下均相似增加。总之，在禁食的最初几小时内，全身能量应激似乎不会影响人体骨骼肌信号、mRNA/蛋白质表达和底物储存。
