Guan Dongyin, Lazar Mitchell A
Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas.
Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Semin Liver Dis. 2022 May;42(2):113-121. doi: 10.1055/a-1792-4240. Epub 2022 Mar 9.
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.
昼夜节律是生理过程、基因表达和行为中约24小时的变化周期。它们是内部生物钟与日常环境节律相互作用的结果,日常环境节律包括光/暗和进食/禁食。请注意,肝脏代谢过程的24小时节律已为人所知近100年。现代研究表明,与代谢一样,肝脏基因表达具有高度节律性。遗传或环境变化会扰乱肝脏的昼夜节律,导致代谢紊乱和肝细胞癌。在本综述中,我们总结了目前对肝脏节律性基因表达调控机制的理解,强调了构成核心生物钟分子的转录因子以及非经典调节因子的作用。我们强调肝脏昼夜节律的可塑性,因为它对来自外部和内部环境的多种输入做出反应,以及昼夜医学对肝脏相关疾病产生影响的潜力。