Two weeks of high-intensity interval training increases skeletal muscle mitochondrial respiration via complex-specific remodeling in sedentary humans. Two weeks of high-intensity interval training increases skeletal muscle mitochondrial respiration via complex-specific remodeling in sedentary humans

Aerobic training remodels the quantity and quality (function per unit) of skeletal muscle mitochondria to promote substrate oxidation, however, there remain key gaps in understanding the underlying mechanisms during initial training adaptations. We used short-term high-intensity interval training (HIIT) to determine changes to mitochondrial respiration and regulatory pathways that occur early in remodeling. Fifteen normal-weight sedentary adults started seven sessions of HIIT over fourteen days and fourteen participants completed the intervention. We collected vastus lateralis biopsies before and 48-hours after HIIT to determine mitochondrial respiration, RNA sequencing, and western blotting for proteins of mitochondrial respiration and degradation via autophagy. HIIT increased respiration per mitochondrial protein for lipid (+23% P=0.020), complex I (+18%, P=0.0015), complex I+II (+14%, P<0.0001) and complex II (+24% P<0.0001). Transcripts that increased with HIIT identified several gene sets of mitochondrial respiration, particularly for complex I, while transcripts that decreased identified pathways of DNA and chromatin remodeling. HIIT lowered protein abundance of autophagy markers for p62 (-19%, P=0.012) and LC3 II/I (-20%, P=0.004) in whole-tissue lysates but not isolated mitochondria. Meal tolerance testing revealed HIIT increased the change in whole-body respiratory exchange ratio and lowered cumulative plasma insulin concentrations. Gene transcripts and respiratory function indicate remodeling of mitochondria within 2 weeks of HIIT. Overall changes are consistent with increased protein quality driving rapid improvements in substrate oxidation. Overall design: 15 normal-weight, sedentary humans, age 18-45 years, completed 2 weeks of high intensity interval training (HIIT). HIIT was completed every other day for 7 sessions and included 10 1-minute bouts of exercise (~90% VO2max) followed by 1 minute rest. Muscle biopsies were acquired before, and 48 hours after, exercise training. Muscle biopsies were subjected to RNA-sequencing.

有氧运动训练可重塑骨骼肌线粒体的数量与质量（单位功能），以促进底物氧化，但目前在理解训练初期适应的潜在机制方面仍存在关键空白。本研究采用短期高强度间歇训练（high-intensity interval training, HIIT），探究重塑早期线粒体呼吸功能与调控通路的变化。本研究纳入15名体重正常的久坐成年人，受试者在14天内完成7次HIIT训练，最终14人完成全部干预流程。我们在HIIT训练前及训练后48小时采集股外侧肌（vastus lateralis）活检样本，以检测线粒体呼吸功能、开展RNA测序，并针对线粒体呼吸相关蛋白及自噬（autophagy）介导的降解蛋白进行免疫印迹实验（western blotting）。结果显示，HIIT可提升每单位线粒体蛋白的呼吸活性：脂质底物呼吸提升23%（P=0.020），线粒体呼吸链复合体I（complex I）呼吸提升18%（P=0.0015），复合体I+II呼吸提升14%（P<0.0001），复合体II（complex II）呼吸提升24%（P<0.0001）。HIIT上调的转录本富集了多条线粒体呼吸相关基因集，尤以复合体I相关基因为著；而下调的转录本则富集DNA与染色质重塑通路。在全组织裂解液中，HIIT可降低自噬标志物p62的蛋白丰度（下降19%，P=0.012）以及LC3 II/I比值（下降20%，P=0.004），但在分离的线粒体组分中未观察到该变化。膳食耐受试验结果显示，HIIT可提升全身呼吸交换比的变化幅度，并降低血浆胰岛素累积浓度。转录组与呼吸功能检测结果表明，HIIT干预2周内即可发生线粒体重塑；整体变化趋势与蛋白质量提升可快速改善底物氧化能力的结论相符。实验设计概况：本研究纳入15名年龄18~45岁、体重正常的久坐成年人，完成为期2周的高强度间歇训练（HIIT）。训练采用隔日进行的方案，共7个疗程，每个疗程包含10组1分钟的全力运动（约相当于个体最大摄氧量的90%，~90% VO2max），组间休息1分钟。分别在训练前及训练后48小时采集股外侧肌活检样本，对样本进行RNA测序分析。