Regulatory Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21453-8. doi: 10.1073/pnas.0909591106. Epub 2009 Nov 25.
In mammals, the circadian oscillator generates approximately 24-h rhythms in feeding behavior, even under constant environmental conditions. Livers of mice held under constant darkness exhibit circadian rhythm in abundance in up to 15% of expressed transcripts. Therefore, oscillations in hepatic transcripts could be driven by rhythmic food intake or sustained by the hepatic circadian oscillator, or a combination of both. To address this question, we used distinct feeding and fasting paradigms on wild-type (WT) and circadian clock-deficient mice. We monitored temporal patterns of feeding and hepatic transcription. Both food availability and the temporal pattern of feeding determined the repertoire, phase, and amplitude of the circadian transcriptome in WT liver. In the absence of feeding, only a small subset of transcripts continued to express circadian patterns. Conversely, temporally restricted feeding restored rhythmic transcription of hundreds of genes in oscillator-deficient mouse liver. Our findings show that both temporal pattern of food intake and the circadian clock drive rhythmic transcription, thereby highlighting temporal regulation of hepatic transcription as an emergent property of the circadian system.
在哺乳动物中，即使在恒定的环境条件下，生物钟振荡器也会产生大约 24 小时的进食行为节律。在持续黑暗环境下饲养的小鼠肝脏中，多达 15%的表达转录本表现出昼夜节律。因此，肝转录本的波动可能是由有节奏的进食驱动的，或者由肝脏生物钟振荡器维持，或者两者兼有。为了解决这个问题，我们使用了野生型（WT）和生物钟缺陷小鼠的不同进食和禁食范式。我们监测了进食和肝转录的时间模式。食物的可获得性和进食的时间模式决定了 WT 肝脏中生物钟转录组的范围、相位和振幅。在没有进食的情况下，只有一小部分转录本继续表达昼夜节律模式。相反，时间限制的进食恢复了时钟缺陷小鼠肝脏中数百个基因的节律性转录。我们的研究结果表明，食物摄入的时间模式和生物钟都驱动着转录的节律性，从而突出了肝脏转录的时间调节作为生物钟系统的一个涌现特性。
