目的:昼夜节律紊乱与代谢紊乱相关,代谢紊乱可导致肥胖和2型糖尿病(T2DM)。在骨骼肌中,氧化能力的降低也与T2DM的发展有关。然而,到目前为止,尚未研究骨骼肌的氧化能力是否在人类中表现出昼夜节律。
方法:精益,健康受试者参加标准生活方案,定期进餐,身体活动和睡眠来反映我们的日常生活方式。在24小时内的五个时间点进行的骨骼肌活检中检查了线粒体氧化能力。
结果:夜间核心体温较低,确认正常的昼夜节奏。骨骼肌氧化能力表现出强劲的昼夜节律,在ADP刺激的呼吸中具有显著的时间效应(状态3MO,状态3MOG和状态3MOGS,p<0.05)。呼吸在下午1点最低,在晚上11点最高(状态3MOGS:80.6±4.0vs.95.8±4.7pmol/mg/s)。有趣的是,线粒体功能的波动也在全身能量消耗中观察到,峰值能量消耗在晚上11点,最低能量消耗在凌晨4点(p<0.001)。此外,我们证明了人骨骼肌中分子钟基因mRNA表达的节律性。
结论:我们的结果表明,生物钟驱动人体骨骼肌氧化代谢的强健节律。人们很容易推测这些节律的中断会导致与昼夜节律失调相关的代谢健康恶化。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.