Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity.

A disturbed day-night rhythm is associated with metabolic perturbations that can lead to obesity and type 2 diabetes mellitus (T2DM). In skeletal muscle, a reduced oxidative capacity is also associated with the development of T2DM. However, whether oxidative capacity in skeletal muscle displays a day-night rhythm in humans has so far not been investigated. Lean, healthy subjects were enrolled in a standardized living protocol with regular meals, physical activity and sleep to reflect our everyday lifestyle. Mitochondrial oxidative capacity was examined in skeletal muscle biopsies taken at five time points within a 24-hour period. Core-body temperature was lower during the early night, confirming a normal day-night rhythm. Skeletal muscle oxidative capacity demonstrated a robust day-night rhythm, with a significant time effect in ADP-stimulated respiration (state 3 MO, state 3 MOG and state 3 MOGS, p < 0.05). Respiration was lowest at 1 PM and highest at 11 PM (state 3 MOGS: 80.6 ± 4.0 vs. 95.8 ± 4.7 pmol/mg/s). Interestingly, the fluctuation in mitochondrial function was also observed in whole-body energy expenditure, with peak energy expenditure at 11 PM and lowest energy expenditure at 4 AM (p < 0.001). In addition, we demonstrate rhythmicity in mRNA expression of molecular clock genes in human skeletal muscle. Our results suggest that the biological clock drives robust rhythms in human skeletal muscle oxidative metabolism. It is tempting to speculate that disruption of these rhythms contribute to the deterioration of metabolic health associated with circadian misalignment. Mitochondrial oxidative capacity in human skeletal muscle follows a day-night rhythm. Oxidative capacity peaks in the late evening and is lowest in the early afternoon. Energy expenditure follows a day-night rhythm and is highest in the late evening. Human muscle exhibits rhythmic gene expression, with a cycling core molecular clock.

紊乱的昼夜节律与可能导致肥胖和2型糖尿病（T2DM）的代谢紊乱有关。在骨骼肌中，氧化能力降低也与T2DM的发展有关。然而，到目前为止，人类骨骼肌的氧化能力是否呈现昼夜节律尚未得到研究。 消瘦的健康受试者被纳入一项标准化的生活方案，包括规律的饮食、身体活动和睡眠，以反映我们的日常生活方式。在24小时内的五个时间点采集骨骼肌活检样本，检测线粒体氧化能力。 核心体温在夜间早些时候较低，证实了正常的昼夜节律。骨骼肌氧化能力呈现出明显的昼夜节律，在ADP刺激的呼吸作用（状态3 MO、状态3 MOG和状态3 MOGS，p < 0.05）中具有显著的时间效应。呼吸作用在下午1点最低，晚上11点最高（状态3 MOGS：80.6 ± 4.0对95.8 ± 4.7 pmol/mg/s）。有趣的是，在全身能量消耗中也观察到了线粒体功能的波动，能量消耗在晚上11点达到峰值，在凌晨4点最低（p < 0.001）。此外，我们证明了人类骨骼肌中分子时钟基因的mRNA表达具有节律性。 我们的研究结果表明，生物钟驱动人类骨骼肌氧化代谢的强烈节律。很容易推测，这些节律的破坏会导致与昼夜节律失调相关的代谢健康恶化。 人类骨骼肌中的线粒体氧化能力遵循昼夜节律。 氧化能力在傍晚达到峰值，在下午早些时候最低。 能量消耗遵循昼夜节律，在傍晚最高。 人类肌肉表现出节律性基因表达，具有循环的核心分子时钟。