Department of Neuroscience and Institute for Behavioral Medicine Research, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
J Biol Rhythms. 2013 Aug;28(4):262-71. doi: 10.1177/0748730413493862.
With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms that are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electric lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however, the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to dim light at night and investigated changes in the circadian system and metabolism. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night altered core circadian clock rhythms in the hypothalamus at both the gene and protein level. Circadian rhythms in clock expression persisted during light at night; however, the amplitude of Per1 and Per2 rhythms was attenuated in the hypothalamus. Circadian oscillations were also altered in peripheral tissues critical for metabolic regulation. Exposure to dimly illuminated, as compared to dark, nights decreased the rhythmic expression in all but one of the core circadian clock genes assessed in the liver. Additionally, mice exposed to dim light at night attenuated Rev-Erb expression in the liver and adipose tissue. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide evidence that mild changes in environmental lighting can alter circadian and metabolic function. Detailed analysis of temporal changes induced by nighttime light exposure may provide insight into the onset and progression of obesity and metabolic syndrome, as well as other disorders involving sleep and circadian rhythm disruption.
除高纬度地区外,生命都是在昼夜分明的环境中进化的。大多数生物已经进化出内在驱动的昼夜节律,与这种日常的明暗循环同步。近年来,人类已经摆脱了自然发生的太阳光照周期,转而采用人工照明,有时还采用由电灯产生的不规则光照时间表。接触不自然的光照周期与肥胖和代谢综合征的发病率增加有关;然而,环境光照改变代谢的方式还知之甚少。因此,我们让老鼠在夜间接受暗光照射,并研究昼夜节律系统和代谢的变化。在这里,我们报告说,夜间接受生态相关水平的暗光(5 勒克斯)照射会改变下丘脑核心生物钟的基因和蛋白质水平。时钟表达的昼夜节律在夜间有光时仍然存在;然而,下丘脑 Per1 和 Per2 节律的振幅减弱。对代谢调节至关重要的外周组织的昼夜节律也发生了改变。与黑暗相比,夜间接受昏暗照明会降低肝脏中评估的核心生物钟基因中除一个以外的所有基因的节律表达。此外,夜间接受暗光照射的老鼠会减弱肝脏和脂肪组织中 Rev-Erb 的表达。昼夜节律的变化与摄食行为的时间变化和体重增加有关。这些结果意义重大,因为它们提供了证据表明,环境光照的微小变化可以改变昼夜节律和代谢功能。对夜间光照引起的时间变化的详细分析可能为肥胖和代谢综合征以及其他涉及睡眠和昼夜节律紊乱的疾病的发病和进展提供线索。