Chronic phase advance alters circadian physiological rhythms and peripheral molecular clocks.
Chronic phase advance alters circadian physiological rhythms and peripheral molecular clocks.
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慢性期提前改变昼夜节律生理节律和外周分子时钟。
DOI：
10.1152/japplphysiol.01139.2012
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Esser,KarynA
中科院分区：
文献类型：
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作者：
Wolff,Gretchen;Duncan,MarilynJ;Esser,KarynA
改变光照的开始，无论是急性还是慢性，都能深刻影响哺乳动物对感染、肿瘤进展、代谢性疾病的发展和死亡率的反应。迄今为止，大多数相移研究都集中在急性暴露于光周期时间变化的情况下，而慢性相移对骨骼肌等外周组织分子节律的影响尚未得到研究。在本研究中，我们在两种表型不同的骨骼肌中测试了慢性相位推进对分子钟机制的影响。阶段推进方案（CPA）涉及每4天6小时的阶段推进（早期轻发作），持续8周。通过生物发光记录对比目鱼肌、指短屈肌（FDB）和肺的分子钟进行分析表明，CPA在CPA之后立即进行研究时，可以使节律期提前。然而，如果在CPA后将小鼠置于自由奔跑状态（DD） 2周，两组肌肉中的分子钟没有相移，但肺中的分子钟仍有相移。CPA小鼠转轮跑行为保持节律性；而自由奔跑节律的内源性周期长度明显短于对照小鼠。核心体温、笼内活动和心率在整个实验过程中都保持有节奏，尽管CPA明显延迟了节律的开始。这些结果提供了与慢性环境不同步相关的生活方式的线索，例如轮班工作，可以对外周组织（包括两种类型的骨骼肌）的分子钟机制产生破坏性影响。从长期来看，这是否会增加胰岛素抵抗/代谢疾病的发病率，还需要进一步研究。
Shifting the onset of light, acutely or chronically, can profoundly affect responses to infection, tumor progression, development of metabolic disease, and mortality in mammals. To date, the majority of phase-shifting studies have focused on acute exposure to a shift in the timing of the light cycle, whereas the consequences of chronic phase shifts alone on molecular rhythms in peripheral tissues such as skeletal muscle have not been studied. In this study, we tested the effect of chronic phase advance on the molecular clock mechanism in two phenotypically different skeletal muscles. The phase advance protocol (CPA) involved 6-h phase advances (earlier light onset) every 4 days for 8 wk. Analysis of the molecular clock, via bioluminescence recording, in the soleus and flexor digitorum brevis (FDB) muscles and lung demonstrated that CPA advanced the phase of the rhythm when studied immediately after CPA. However, if the mice were placed into free-running conditions (DD) for 2 wk after CPA, the molecular clock was not phase shifted in the two muscles but was still shifted in the lung. Wheel running behavior remained rhythmic in CPA mice; however, the endogenous period length of the free-running rhythm was significantly shorter than that of control mice. Core body temperature, cage activity, and heart rate remained rhythmic throughout the experiment, although the onset of the rhythms was significantly delayed with CPA. These results provide clues that lifestyles associated with chronic environmental desynchrony, such as shift work, can have disruptive effects on the molecular clock mechanism in peripheral tissues, including both types of skeletal muscle. Whether this can contribute, long term, to increased incidence of insulin resistance/metabolic disease requires further study.