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(2022-08-03 00:15):
#paper doi:10.1016/j.molmet.2022.101556 Molecular Metabolism, Tryptophan Metabolism is a Physiological Integrator Regulating Circadian Rhythms. 这是个关于昼夜节律生物钟的研究，比较经典的基于动物模型的生理学研究实验。通过对小鼠进行特定光照条件（12小时昼夜平分，或24小时全黑暗环境）饲养，使其适应该节律。之后通过控制饮食，减少或去除必需氨基酸的摄入，再改变特定光照条件，研究其对节律恢复的影响。根据小鼠的活动时间记录，研究其所表现出的节律，即生物钟调节结果。通过采集小鼠血液、肝脏组织等样本，进行质谱、液相色谱、转录组测序等检测。最终证明色氨酸代谢是关键的昼夜节律调节剂，其代谢受到光调控，并影响小鼠的昼夜节律调节。
Abstract:
OBJECTIVE: The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known …
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OBJECTIVE: The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of essential amino acids.METHODS: Mice were fed diets depleted of specific essential amino acids and their behavioral rhythms were monitored and tryptophan was selected for downstream analyses. The role of tryptophan metabolism in modulating circadian homeostasis was studied using isotope tracing as well as transcriptomic- and metabolomic- analyses.RESULTS: Dietary tryptophan depletion alters behavioral rhythms in mice. Furthermore, tryptophan metabolism was shown to be regulated in a time- and light- dependent manner. A multi-omics approach and combinatory diet/light interventions demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver.CONCLUSIONS: Tryptophan metabolism is a modulator of circadian homeostasis by integrating environmental cues. Our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.
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