Semin Liver Dis 2022; 42(02): 113-121
DOI: 10.1055/a-1792-4240
Review Article

Circadian Regulation of Gene Expression and Metabolism in the Liver

Dongyin Guan
1   Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas
Mitchell A. Lazar
2   Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
3   Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
4   Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
› Author Affiliations
Funding This work was supported by the JPB Foundation (M.A.L.), the Cox Medical Research Institute (M.A.L.), Cancer Prevention and Research Institute of Texas (RR210029, D.G.), as well as by National Institutes of Health grants (R01-DK045586, M.A.L.; and K01-DK125602, D.G.).


Circadian rhythms are approximately 24-hour cycles of variation in physiological processes, gene expression, and behavior. They result from the interplay of internal biological clocks with daily environmental rhythms, including light/dark and feeding/fasting. Note that 24-hour rhythms of liver metabolic processes have been known for almost 100 years. Modern studies reveal that, like metabolism, hepatic gene expression is highly rhythmic. Genetic or environmental changes can disrupt the circadian rhythms of the liver, leading to metabolic disorders and hepatocellular carcinoma. In this review, we summarize the current understanding of mechanisms regulating rhythmic gene expression in the liver, highlighting the roles of transcription factors that comprise the core clock molecular as well as noncanonical regulators. We emphasize the plasticity of circadian rhythms in the liver as it responds to multiple inputs from the external and internal environments as well as the potential of circadian medicine to impact liver-related diseases.

Publication History

Accepted Manuscript online:
09 March 2022

Article published online:
23 June 2022

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