Tahara Yu, Ding Jingwei, Ito Akito, Shibata Shigenobu
Department of Public Health and Health Policy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-0037, Japan.
School of Advanced Science and Engineering, Waseda University, Shinjuku-ku, Tokyo, 162-0056, Japan.
NPJ Sci Food. 2024 Aug 19;8(1):51. doi: 10.1038/s41538-024-00295-6.
Caffeine consumption is associated with the evening chronotype, and caffeine administration in mice results in prolonged period of the circadian rhythm in locomotor activity. However, as caffeine is bitter, sweetened caffeine is preferred by humans and mice; yet, its impact on the circadian clock has not been explored. In this study, mice were provided with freely available sweetened caffeine to investigate its effects on behavioral rhythms and peripheral clocks. Mice that freely consumed sweetened caffeine shifted from nocturnal to diurnal activity rhythms. In addition to the light-dark entrained behavioral rhythm component, some animals exhibited free-running period longer than 24-h. Intraperitoneal administration of caffeine at the beginning of the light phase also acutely induced diurnal behavior. The behavioral rhythms with long period (26-30 h) due to sweetened caffeine were observed even in mice housed under constant light or with a lesioned central circadian clock located in the suprachiasmatic nucleus of the hypothalamus; however, the rhythmicity was unstable. PER2::LUCIFERASE rhythms in peripheral tissues, such as the kidney, as measured via in vivo whole-body imaging during caffeine consumption, showed reduced amplitude and desynchronized phases among individuals. These results indicate that consumption of sweetened caffeine induces diurnal and long-period behavioral rhythms irrespective of the central clock, causing desynchronization of the clock in the body.
咖啡因的摄入与晚型昼夜节律相关，给小鼠注射咖啡因会导致其运动活动的昼夜节律周期延长。然而，由于咖啡因味道苦涩，加了甜味剂的咖啡因更受人类和小鼠青睐；不过，其对生物钟的影响尚未得到研究。在本研究中，给小鼠提供可自由获取的加了甜味剂的咖啡因，以研究其对行为节律和外周生物钟的影响。自由摄入加了甜味剂的咖啡因的小鼠从夜间活动节律转变为白天活动节律。除了受明暗周期影响的行为节律成分外，一些动物还表现出自由运转周期超过24小时。在光照阶段开始时腹腔注射咖啡因也会急性诱导白天行为。即使在持续光照或下丘脑视交叉上核中的中央生物钟受损的小鼠中，也观察到了因加了甜味剂的咖啡因导致的长周期（26 - 30小时）行为节律；然而，这种节律性并不稳定。在摄入咖啡因期间通过体内全身成像测量的外周组织（如肾脏）中的PER2::荧光素酶节律，显示个体间振幅降低且相位不同步。这些结果表明，摄入加了甜味剂的咖啡因会诱导白天和长周期行为节律，而与中央生物钟无关，从而导致体内生物钟不同步。
