BGES Department, Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, USA.
Barshop Institute for Aging and Longevity Studies, UTHSCSA, San Antonio, TX, USA.
FASEB J. 2021 May;35(5):e21590. doi: 10.1096/fj.202100116R.
Light is the key regulator of circadian clock, the time-keeping system synchronizing organism physiology and behavior with environmental day and night conditions. In its natural habitat, the strictly subterranean naked mole-rat (Heterocephalus glaber) has lived in a light-free environment for millennia. We questioned if this species retains a circadian clock and if the patterns of this clock and concomitant rhythms differed in liver tissue from mice and naked mole-rats. As expected, in mice, the various circadian clock genes peaked at different times of the day; the Period gene (Per) group peaked in the evening, whereas Brain and Muscle ARNT-like1 (Bmal1) gene peaked in the morning; this phase shift is considered to be fundamental for circadian clock function. In sharp contrast, in the naked mole-rat both Per1 and Per2, as well as Bmal1, peaked at the same time in the morning-around ZT2-suggesting the organization of the molecular circadian oscillator was different. Moreover, gene expression rhythms associated with glucose metabolism and mTOR signaling also differed between the species. Although the activity of mTORC1 was lower, while that of mTORC2 was higher in naked mole-rat livers compared to mice, unlike that of mice where the expression profiles of glucose metabolism genes were not synchronized, these were highly synchronized in naked mole-rats and likely linked to their use of feeding times at zeitgebers.
光是生物钟的关键调节因子，生物钟使生物的生理和行为与环境的昼夜条件同步。在其天然栖息地，严格的地下裸鼹鼠（Heterocephalus glaber）已经在无光的环境中生活了数千年。我们质疑该物种是否保留了生物钟，如果是，那么生物钟及其伴随的节律在肝脏组织中的模式是否与小鼠和裸鼹鼠不同。正如预期的那样，在小鼠中，各种生物钟基因在一天中的不同时间达到峰值；Period 基因（Per）组在晚上达到峰值，而 Brain and Muscle ARNT-like1（Bmal1）基因在早上达到峰值；这种相位转移被认为是生物钟功能的基础。相比之下，在裸鼹鼠中，Per1 和 Per2 以及 Bmal1 都在早上同一时间达到峰值——大约在 ZT2 左右——这表明分子生物钟振荡器的组织方式不同。此外，与葡萄糖代谢和 mTOR 信号相关的基因表达节律也在两种物种之间存在差异。尽管与小鼠相比，裸鼹鼠肝脏中的 mTORC1 活性较低，而 mTORC2 活性较高，但与小鼠不同的是，小鼠中葡萄糖代谢基因的表达谱没有同步，这些在裸鼹鼠中高度同步，可能与它们利用时间作为同步信号有关。
