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Deconstructing circadian disruption: Assessing the contribution of reduced peripheral oscillator amplitude on obesity and glucose intolerance in mice.
Journal of Pineal Research ( IF 8.3 ) Pub Date : 2020-04-03 , DOI: 10.1111/jpi.12654
Vincent van der Vinne 1 , Blanca Martin Burgos 2 , Mary E Harrington 2 , David R Weaver 1
Affiliation  

Disturbing the circadian regulation of physiology by disruption of the rhythmic environment is associated with adverse health outcomes but the underlying mechanisms are unknown. Here, the response of central and peripheral circadian clocks to an advance or delay of the light‐dark cycle was determined in mice. This identified transient damping of peripheral clocks as a consequence of an advanced light‐dark cycle. Similar depression of peripheral rhythm amplitude was observed in mice exposed to repeated phase shifts. To assess the metabolic consequences of such peripheral amplitude depression in isolation, temporally chimeric mice lacking a functional central clock (Vgat‐Cre+ Bmal1fl/fl ) were housed in the absence of environmental rhythmicity. In vivo PER2::LUC bioluminescence imaging of anesthetized and freely moving mice revealed that this resulted in a state of peripheral amplitude depression, similar in severity to that observed transiently following an advance of the light‐dark cycle. Surprisingly, our mice did not show alterations in body mass or glucose tolerance in males or females on regular or high‐fat diets. Overall, our results identify transient damping of peripheral rhythm amplitude as a consequence of exposure to an advanced light‐dark cycle but chronic damping of peripheral clocks in isolation is insufficient to induce adverse metabolic outcomes in mice.

中文翻译:

解构昼夜节律紊乱:评估外周振荡器振幅降低对小鼠肥胖和葡萄糖耐受不良的影响。

通过破坏有节奏的环境来扰乱生理的昼夜节律调节与不利的健康结果有关,但潜在的机制尚不清楚。在这里,在小鼠中确定了中枢和外周生物钟对明暗周期提前或延迟的反应。这将外围时钟的瞬态阻尼识别为先进的明暗循环的结果。在暴露于重复相移的小鼠中观察到类似的外周节律幅度下降。为了单独评估这种外周振幅抑制的代谢后果,缺乏功能性中央时钟的时间嵌合小鼠 ( Vgat-Cre + Bmal1 fl/fl ) 被安置在没有环境节奏的情况下。麻醉和自由移动小鼠的体内 PER2::LUC 生物发光成像显示,这导致了外周振幅降低的状态,其严重程度与在明暗循环推进后短暂观察到的情况相似。令人惊讶的是,我们的小鼠在常规或高脂肪饮食的雄性或雌性中没有表现出体重或葡萄糖耐量的变化。总体而言,我们的结果确定了由于暴露于先进的明暗循环而导致的外周节律幅度的瞬时阻尼,但孤立的外周时钟的慢性阻尼不足以引起小鼠的不良代谢结果。
更新日期:2020-04-03
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