Circadian Regulation of Gene Expression and Metabolism in the Liver

Overview

Journal Semin Liver Dis

Publisher Thieme

Specialty Gastroenterology

Date 2022 Mar 9

PMID 35263797

Authors

Dongyin Guan

Mitchell A Lazar

Affiliations

Soon will be listed here.

Abstract

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.

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References

Yeung J, Mermet J, Jouffe C, Marquis J, Charpagne A, Gachon F . Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs. Genome Res. 2017; 28(2):182-191. PMC: 5793782. DOI: 10.1101/gr.222430.117. View

Wu S, Mar-Heyming R, Dugum E, Kolaitis N, Qi H, Pajukanta P . Upstream transcription factor 1 influences plasma lipid and metabolic traits in mice. Hum Mol Genet. 2009; 19(4):597-608. PMC: 2807368. DOI: 10.1093/hmg/ddp526. View

Byun J, Choi Y, Kang Y, Jang B, Kang K, Jeon Y . Retinoic acid-related orphan receptor alpha reprograms glucose metabolism in glutamine-deficient hepatoma cells. Hepatology. 2014; 61(3):953-64. DOI: 10.1002/hep.27577. View

Shimomura K, Kumar V, Koike N, Kim T, Chong J, Buhr E . Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice. Elife. 2013; 2:e00426. PMC: 3622178. DOI: 10.7554/eLife.00426. View

Hassan S, Ali A, Yassine M, Sohn D, Pfeffer M, Janicke R . Relationship between locomotor activity rhythm and corticosterone levels during HCC development, progression, and treatment in a mouse model. J Pineal Res. 2021; 70(3):e12724. DOI: 10.1111/jpi.12724. View

Le Minh N, Damiola F, Tronche F, Schutz G, Schibler U . Glucocorticoid hormones inhibit food-induced phase-shifting of peripheral circadian oscillators. EMBO J. 2001; 20(24):7128-36. PMC: 125339. DOI: 10.1093/emboj/20.24.7128. View

Hassan S, Schmithals C, von Harten M, Piiper A, Korf H, von Gall C . Time-dependent changes in proliferation, DNA damage and clock gene expression in hepatocellular carcinoma and healthy liver of a transgenic mouse model. Int J Cancer. 2020; 148(1):226-237. DOI: 10.1002/ijc.33228. View

Koike N, Yoo S, Huang H, Kumar V, Lee C, Kim T . Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science. 2012; 338(6105):349-54. PMC: 3694775. DOI: 10.1126/science.1226339. View

Johnson T, Zhang X, Shi S, Umbenhauer D . Statins and PPARalpha agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment. Toxicol Appl Pharmacol. 2005; 208(3):210-21. DOI: 10.1016/j.taap.2005.03.004. View

10.

Bass J, Lazar M . Circadian time signatures of fitness and disease. Science. 2016; 354(6315):994-999. DOI: 10.1126/science.aah4965. View

11.

Weger B, Gobet C, David F, Atger F, Martin E, Phillips N . Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms. Proc Natl Acad Sci U S A. 2021; 118(3). PMC: 7826335. DOI: 10.1073/pnas.2015803118. View

12.

Imaizumi H, Takahashi A, Tanji N, Abe K, Sato Y, Anzai Y . The Association between Sleep Duration and Non-Alcoholic Fatty Liver Disease among Japanese Men and Women. Obes Facts. 2015; 8(4):234-42. PMC: 5644852. DOI: 10.1159/000436997. View

13.

Storch K, Lipan O, Leykin I, Viswanathan N, Davis F, Wong W . Extensive and divergent circadian gene expression in liver and heart. Nature. 2002; 417(6884):78-83. DOI: 10.1038/nature744. View

14.

Vollmers C, Gill S, DiTacchio L, Pulivarthy S, Le H, Panda S . Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proc Natl Acad Sci U S A. 2009; 106(50):21453-8. PMC: 2795502. DOI: 10.1073/pnas.0909591106. View

15.

Levine D, Hong H, Weidemann B, Ramsey K, Affinati A, Schmidt M . NAD Controls Circadian Reprogramming through PER2 Nuclear Translocation to Counter Aging. Mol Cell. 2020; 78(5):835-849.e7. PMC: 7275919. DOI: 10.1016/j.molcel.2020.04.010. View

16.

Yin L, Wu N, Curtin J, Qatanani M, Szwergold N, Reid R . Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways. Science. 2007; 318(5857):1786-9. DOI: 10.1126/science.1150179. View

17.

Guan D, Lazar M . Interconnections between circadian clocks and metabolism. J Clin Invest. 2021; 131(15). PMC: 8321578. DOI: 10.1172/JCI148278. View

18.

Zhang Y, Papazyan R, Damle M, Fang B, Jager J, Feng D . The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ. Genes Dev. 2017; 31(12):1202-1211. PMC: 5558923. DOI: 10.1101/gad.302323.117. View

19.

Guan D, Xiong Y, Trinh T, Xiao Y, Hu W, Jiang C . The hepatocyte clock and feeding control chronophysiology of multiple liver cell types. Science. 2020; 369(6509):1388-1394. PMC: 7849028. DOI: 10.1126/science.aba8984. View

20.

Solt L, Griffin P, Burris T . Ligand regulation of retinoic acid receptor-related orphan receptors: implications for development of novel therapeutics. Curr Opin Lipidol. 2010; 21(3):204-11. PMC: 5024716. DOI: 10.1097/MOL.0b013e328338ca18. View