Skip to main content
SpringerLink
Log in
Book cover

Nuclear Receptors in Human Health and Disease pp 143–153Cite as

Circadian Rhythm and Nuclear Receptors

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1390))

Abstract

All life of Earth has evolved mechanisms to track time. This permits anticipation of predictable changes in light/dark, and in most cases also directs fed/fasted cycles, and sleep/wake. The nuclear receptors enjoy a close relationship with the molecular machinery of the clock. Some play a core role within the circadian machinery, other respond to ligands which oscillate in concentration, and physical cross-talk between clock transcription factors, eg cryptochromes, and multiple nuclear receptors also enable coupling of nuclear receptor function to time of day. Essential processes including inflammation, and energy metabolism are strongly regulated by both the circadian machinery, and rhythmic behaviour, and also by multiple members of the nuclear receptor family. An emerging theme is reciprocal regulation of key processes by different members of the nuclear receptor family, for example NR1D1/2, and NR1F1, in regulation of the core circadian clock transcription factor BMAL1.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Allada R, Bass J (2021) Circadian mechanisms in medicine. N Engl J Med 384:550–561. https://doi.org/10.1056/NEJMra1802337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Yang X, Lamia KA, Evans RM (2007) Nuclear receptors, metabolism, and the circadian clock. Cold Spring Harb Symp Quant Biol 72:387–394. https://doi.org/10.1101/sqb.2007.72.058

    Article  CAS  PubMed  Google Scholar 

  3. Yang X et al (2006) Nuclear receptor expression links the circadian clock to metabolism. Cell 126:801–810

    Article  CAS  Google Scholar 

  4. Zhang R, Lahens NF, Ballance HI, Hughes ME, Hogenesch JB (2014) A circadian gene expression atlas in mammals: implications for biology and medicine. Proc Natl Acad Sci U S A 111:16219–16224. https://doi.org/10.1073/pnas.1408886111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Koike N et al (2012) Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science 338:349–354. https://doi.org/10.1126/science.1226339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kriebs A et al (2017) Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors and modulate transcriptional activity. Proc Natl Acad Sci U S A 114:8776–8781. https://doi.org/10.1073/pnas.1704955114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Caratti G et al (2018) REVERBa couples the circadian clock to hepatic glucocorticoid action. J Clin Invest 128:4454–4471. https://doi.org/10.1172/JCI96138

    Article  PubMed  PubMed Central  Google Scholar 

  8. Schmutz I, Ripperger JA, Baeriswyl-Aebischer S, Albrecht U (2010) The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors. Genes Dev 24:345–357. https://doi.org/10.1101/gad.564110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Carter SJ et al (2016) A matter of time: study of circadian clocks and their role in inflammation. J Leukoc Biol 99:549–560. https://doi.org/10.1189/jlb.3RU1015-451R

    Article  CAS  PubMed  Google Scholar 

  10. Jagannath A et al (2021) Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice. Nat Commun 12:2113. https://doi.org/10.1038/s41467-021-22179-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Foster RG, Hankins MW, Peirson SN (2007) Light, photoreceptors, and circadian clocks. Methods Mol Biol 362:3–28. https://doi.org/10.1007/978-1-59745-257-1_1

    Article  CAS  PubMed  Google Scholar 

  12. Foster RG, Helfrich-Forster C (2001) The regulation of circadian clocks by light in fruitflies and mice. Philos Trans R Soc Lond Ser B Biol Sci 356:1779–1789. https://doi.org/10.1098/rstb.2001.0962

    Article  CAS  Google Scholar 

  13. Takahashi JS (2017) Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet 18:164–179. https://doi.org/10.1038/nrg.2016.150

    Article  CAS  PubMed  Google Scholar 

  14. Balsalobre A et al (2000) Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 289:2344–2347

    Article  CAS  Google Scholar 

  15. Cho H et al (2012) Regulation of circadian behaviour and metabolism by REV-ERB-alpha and REV-ERB-beta. Nature 485:123–127

    Article  CAS  Google Scholar 

  16. Preitner N et al (2002) The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110:251–260. https://doi.org/10.1016/s0092-8674(02)00825-5

    Article  CAS  PubMed  Google Scholar 

  17. Sinturel F et al (2021) Circadian hepatocyte clocks keep synchrony in the absence of a master pacemaker in the suprachiasmatic nucleus or other extrahepatic clocks. Genes Dev 35:329–334. https://doi.org/10.1101/gad.346460.120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Schibler U et al (2015) Clock-talk: interactions between central and peripheral circadian oscillators in mammals. Cold Spring Harb Symp Quant Biol 80:223–232. https://doi.org/10.1101/sqb.2015.80.027490

    Article  PubMed  Google Scholar 

  19. Gerber A et al (2015) The systemic control of circadian gene expression. Diabetes Obes Metab 17(Suppl 1):23–32. https://doi.org/10.1111/dom.12512

    Article  CAS  PubMed  Google Scholar 

  20. Gerber A et al (2013) Blood-borne circadian signal stimulates daily oscillations in actin dynamics and SRF activity. Cell 152:492–503. https://doi.org/10.1016/j.cell.2012.12.027

    Article  CAS  PubMed  Google Scholar 

  21. Maidstone R et al (2021) Shift work is associated with positive COVID-19 status in hospitalised patients. Thorax 76:601–606. https://doi.org/10.1136/thoraxjnl-2020-216651

    Article  PubMed  Google Scholar 

  22. Maidstone RJ et al (2021) Night shift work is associated with an increased risk of asthma. Thorax 76:53–60. https://doi.org/10.1136/thoraxjnl-2020-215218

    Article  PubMed  Google Scholar 

  23. Daghlas I et al (2019) Sleep duration and myocardial infarction. J Am Coll Cardiol 74:1304–1314. https://doi.org/10.1016/j.jacc.2019.07.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tam SKE et al (2021) Dim light in the evening causes coordinated realignment of circadian rhythms, sleep, and short-term memory. Proc Natl Acad Sci U S A 118. https://doi.org/10.1073/pnas.2101591118

  25. Vetter C et al (2018) Night shift work, genetic risk, and type 2 diabetes in the UK biobank. Diabetes Care 41:762–769. https://doi.org/10.2337/dc17-1933

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pariollaud M, Lamia KA (2020) Cancer in the fourth dimension: what is the impact of circadian disruption? Cancer Discov 10:1455–1464. https://doi.org/10.1158/2159-8290.CD-20-0413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hunter AL et al (2020) Nuclear receptor REVERBα is a state-dependent regulator of liver energy metabolism. Proc Natl Acad Sci U S A 117:25869–25879. https://doi.org/10.1073/pnas.2005330117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Crosby P et al (2019) Insulin/IGF-1 drives PERIOD Synthesis to entrain circadian rhythms with feeding time. Cell 177:896–909 e820. https://doi.org/10.1016/j.cell.2019.02.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Eckel-Mahan KL et al (2013) Reprogramming of the circadian clock by nutritional challenge. Cell 155:1464–1478. https://doi.org/10.1016/j.cell.2013.11.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Preidis GA, Kim KH, Moore DD (2017) Nutrient-sensing nuclear receptors PPARalpha and FXR control liver energy balance. J Clin Invest 127:1193–1201. https://doi.org/10.1172/JCI88893

    Article  PubMed  PubMed Central  Google Scholar 

  31. Goldstein I et al (2017) Transcription factor assisted loading and enhancer dynamics dictate the hepatic fasting response. Genome Res 27:427–439. https://doi.org/10.1101/gr.212175.116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Arble DM et al (2015) Impact of sleep and circadian disruption on energy balance and diabetes: a summary of workshop discussions. Sleep 38:1849–1860. https://doi.org/10.5665/sleep.5226

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dashti HS et al (2015) Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants. Am J Clin Nutr 101:135–143. https://doi.org/10.3945/ajcn.114.095026

    Article  CAS  PubMed  Google Scholar 

  34. Mattson MP et al (2014) Meal frequency and timing in health and disease. Proc Natl Acad Sci U S A 111:16647–16653. https://doi.org/10.1073/pnas.1413965111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wilkinson M et al (2019) Circadian rhythm of exhaled biomarkers in health and asthma. Eur Respir J 54. https://doi.org/10.1183/13993003.01068-2019

  36. Durrington HJ et al (2018) Time of day affects eosinophil biomarkers in asthma: implications for diagnosis and treatment. Am J Respir Crit Care Med 198:1578–1581. https://doi.org/10.1164/rccm.201807-1289LE

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Skene DJ et al (2018) Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. Proc Natl Acad Sci U S A 115:7825–7830. https://doi.org/10.1073/pnas.1801183115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhang Z et al (2019) Genome-wide effect of pulmonary airway epithelial cell-specific Bmal1 deletion. FASEB J 33:6226–6238. https://doi.org/10.1096/fj.201801682R

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. West AC et al (2017) Misalignment with the external light environment drives metabolic and cardiac dysfunction. Nat Commun 8:417. https://doi.org/10.1038/s41467-017-00462-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Chang AM et al (2019) Chronotype genetic variant in PER2 is associated with intrinsic circadian period in humans. Sci Rep 9:5350. https://doi.org/10.1038/s41598-019-41712-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Jones SE et al (2019) Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms. Nat Commun 10:343. https://doi.org/10.1038/s41467-018-08259-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Duez H, Staels B (2008) The nuclear receptors Rev-erbs and RORs integrate circadian rhythms and metabolism. Diab Vasc Dis Res 5:82–88

    Article  Google Scholar 

  43. He B et al (2016) The small molecule Nobiletin targets the molecular oscillator to enhance circadian rhythms and protect against metabolic syndrome. Cell Metab 23:610–621. https://doi.org/10.1016/j.cmet.2016.03.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chen Z, Yoo SH, Takahashi JS (2018) Development and therapeutic potential of small-molecule modulators of circadian systems. Annu Rev Pharmacol Toxicol 58:231–252. https://doi.org/10.1146/annurev-pharmtox-010617-052645

    Article  CAS  PubMed  Google Scholar 

  45. Yin L, Wu N, Lazar MA (2010) Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism. Nucl Recept Signal 8:e001

    Article  Google Scholar 

  46. Meng QJ et al (2008) Ligand modulation of REV-ERBalpha function resets the peripheral circadian clock in a phasic manner. J Cell Sci 121:3629–3635. https://doi.org/10.1242/jcs.035048

    Article  CAS  PubMed  Google Scholar 

  47. Trump RP et al (2013) Optimized chemical probes for REV-ERBα. J Med Chem 56:4729–4737. https://doi.org/10.1021/jm400458q

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Solt LA et al (2012) Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature 485:62–68

    Article  CAS  Google Scholar 

  49. Dierickx P et al (2019) SR9009 has REV-ERB-independent effects on cell proliferation and metabolism. Proc Natl Acad Sci U S A 116:12147–12152. https://doi.org/10.1073/pnas.1904226116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhu B et al (2015) Coactivator-dependent oscillation of chromatin accessibility dictates circadian gene amplitude via REV-ERB loading. Mol Cell 60:769–783. https://doi.org/10.1016/j.molcel.2015.10.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ince LM et al (2019) Circadian variation in pulmonary inflammatory responses is independent of rhythmic glucocorticoid signaling in airway epithelial cells. FASEB J 33:126–139. https://doi.org/10.1096/fj.201800026RR

    Article  CAS  PubMed  Google Scholar 

  52. Le Minh N, Damiola F, Tronche F, Schutz G, Schibler U (2001) Glucocorticoid hormones inhibit food-induced phase-shifting of peripheral circadian oscillators. EMBO J 20:7128–7136. https://doi.org/10.1093/emboj/20.24.7128

    Article  PubMed  PubMed Central  Google Scholar 

  53. Gibbs J et al (2014) An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nat Med 20:919–926. https://doi.org/10.1038/nm.3599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dickmeis T et al (2007) Glucocorticoids play a key role in circadian cell cycle rhythms. PLoS Biol 5:e78. https://doi.org/10.1371/journal.pbio.0050078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Weger BD et al (2021) Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms. Proc Natl Acad Sci U S A 118. https://doi.org/10.1073/pnas.2015803118

  56. Jordan SD, Lamia KA (2013) AMPK at the crossroads of circadian clocks and metabolism. Mol Cell Endocrinol 366:163–169. https://doi.org/10.1016/j.mce.2012.06.017

    Article  CAS  PubMed  Google Scholar 

  57. Lamia KA et al (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326:437–440. https://doi.org/10.1126/science.1172156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Masri S et al (2016) Lung adenocarcinoma distally rewires hepatic circadian homeostasis. Cell 165:896–909. https://doi.org/10.1016/j.cell.2016.04.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Blacher E et al (2022) Aging disrupts circadian gene regulation and function in macrophages. Nat Immunol 23:229–236. https://doi.org/10.1038/s41590-021-01083-0

    Article  CAS  PubMed  Google Scholar 

  60. Lamia KA et al (2011) Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature 480:552–556. https://doi.org/10.1038/nature10700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Robles MS, Humphrey SJ, Mann M (2017) Phosphorylation is a central mechanism for circadian control of metabolism and physiology. Cell Metab 25:118–127. https://doi.org/10.1016/j.cmet.2016.10.004

    Article  CAS  PubMed  Google Scholar 

  62. Nader N, Chrousos GP, Kino T (2009) Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications. FASEB J 23:1572–1583. https://doi.org/10.1096/fj.08-117697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Buttgereit F et al (2008) Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial. Lancet 371:205–214

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Oxford, Oxford, UK

    David W. Ray

Authors
  1. David W. Ray
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David W. Ray .

Editor information

Editors and Affiliations

  1. College of Pharmacy, The Ohio State University, Columbus, OH, USA

    Moray J. Campbell

  2. Department of Surgery & Cancer, Imperial College London, London, UK

    Charlotte L. Bevan

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ray, D.W. (2022). Circadian Rhythm and Nuclear Receptors. In: Campbell, M.J., Bevan, C.L. (eds) Nuclear Receptors in Human Health and Disease. Advances in Experimental Medicine and Biology, vol 1390. Springer, Cham. https://doi.org/10.1007/978-3-031-11836-4_8

Download citation

Publish with us

Policies and ethics

Search

Navigation