Misalignment with the external light environment drives metabolic and cardiac dysfunction.
Misalignment with the external light environment drives metabolic and cardiac dysfunction.
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DOI：
10.1038/s41467-017-00462-2
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发表时间：
2017-09-12
影响因子：
16.6
通讯作者：
Bechtold DA
中科院分区：
文献类型：
--
作者：
West AC;Smith L;Ray DW;Loudon ASI;Brown TM;Bechtold DA
大多数生物体使用内部生物钟来将行为和生理过程与昼夜循环的特定阶段相匹配。其核心是跨多个器官系统内部过程的同步。环境不同步（例如轮班工作）深刻影响人类健康，增加心血管疾病和糖尿病风险，但其潜在机制尚不清楚。在这里，我们描述了内部时钟和外部光暗（LD）周期之间的不同步对哺乳动物生理学的影响。我们发现，即使在稳定的LD环境下，相位失调也会产生深远的影响，代谢效率降低，心功能紊乱，包括QT间期持续时间延长。重要的是，生理功能障碍不是由核心时钟功能中断驱动的，也不是由器官之间的内部不同步驱动的，而是由内部时钟和外部环境之间的相位关系改变驱动的。我们认为，相位失调是与轮班工作、生物钟和社交时差相关的病理的主要驱动因素。内部昼夜节律与昼夜周期之间的不一致可能由遗传、行为和环境因素引起，并可能对人体生理产生深远影响。在这里，West等人表明，内部时钟和外部环境之间的不同步改变了小鼠的代谢参数和心功能。
Most organisms use internal biological clocks to match behavioural and physiological processes to specific phases of the day–night cycle. Central to this is the synchronisation of internal processes across multiple organ systems. Environmental desynchrony (e.g. shift work) profoundly impacts human health, increasing cardiovascular disease and diabetes risk, yet the underlying mechanisms remain unclear. Here, we characterise the impact of desynchrony between the internal clock and the external light–dark (LD) cycle on mammalian physiology. We reveal that even under stable LD environments, phase misalignment has a profound effect, with decreased metabolic efficiency and disrupted cardiac function including prolonged QT interval duration. Importantly, physiological dysfunction is not driven by disrupted core clock function, nor by an internal desynchrony between organs, but rather the altered phase relationship between the internal clockwork and the external environment. We suggest phase misalignment as a major driver of pathologies associated with shift work, chronotype and social jetlag. The misalignment between internal circadian rhythm and the day-night cycle can be caused by genetic, behavioural and environmental factors, and may have a profound impact on human physiology. Here West et al. show that desynchrony between the internal clock and the external environment alter metabolic parameters and cardiac function in mice.
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影响因子：
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通讯作者：
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