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Internal circadian clock and liver metabolism

CHEN Ya-Qiong, LIU Ya-Xin, WANG Lei, ZHOU Ling-Qin, LIU Yi*

Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Fudan University, Shanghai 200032, China


Circadian clock is an internal autonomous time-keeping system, including central clocks located in the suprachiasmatic nucleus (SCN) and peripheral clocks. The molecular circadian clock consists of a set of interlocking transcriptional-translational feedback loops that take the clock-controlled genes 24 h to oscillate. The core mechanism of molecular circadian clock is that CLOCK/BMAL1 dimer activates the transcription of cryptochromes (CRYs) and Periods (PERs), which act as transcriptional repressors of further CLOCK/BMAL1-mediated transcription. In addition to this basic clock, there is an additional sub-loop of REV-ERBα and RORα regulating the transcription of BMAL1. Approximately 80% protein-coding genes demonstrate significant rhythmicity. The earth rotation is responsible for the generation of the daily circadian rhythms. To coordinate metabolic balance and energy availability, almost all organisms adapt to the rhythm. Studies have shown that circadian clock integrating with metabolic homeostasis increases the efficiency of energy usage and coordinates with different organs in order to adapt to internal physiology and external environment soon. As the central organ of metabolism, the liver performs various physiological activities nearly all controlled by the circadian clock. There are multiple interactive regulation mechanisms between the circadian clock and the regulation of liver metabolism. The misalignment of metabolism with tissue circadian is identified as a high-risk factor of metabolic diseases. This article reviews the recent studies on circadian physiological regulation of liver glucose, lipid and protein metabolism and emphasizes oscillation of mitochondrial function. We also take an outlook for new methods and application of circadian clock research in the future.

Key words: circadian clock; metabolic homeostasis; liver; circadian rhythm

Received: 2020-11-29  Accepted: 2021-06-04

Corresponding author: LIU Yi  E-mail:

DOI: 10.13294/j.aps.2021.0072

Citing This Article:

CHEN Ya-Qiong, LIU Ya-Xin, WANG Lei, ZHOU Ling-Qin, LIU Yi. Internal circadian clock and liver metabolism. Acta Physiol Sin 2021; 73 (5): 734-744 (in Chinese with English abstract).