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.
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Allada R, Bass J (2021) Circadian mechanisms in medicine. N Engl J Med 384:550–561. https://doi.org/10.1056/NEJMra1802337
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
Yang X et al (2006) Nuclear receptor expression links the circadian clock to metabolism. Cell 126:801–810
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
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
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
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
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
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
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
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
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
Takahashi JS (2017) Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet 18:164–179. https://doi.org/10.1038/nrg.2016.150
Balsalobre A et al (2000) Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 289:2344–2347
Cho H et al (2012) Regulation of circadian behaviour and metabolism by REV-ERB-alpha and REV-ERB-beta. Nature 485:123–127
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Duez H, Staels B (2008) The nuclear receptors Rev-erbs and RORs integrate circadian rhythms and metabolism. Diab Vasc Dis Res 5:82–88
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
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
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
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
Trump RP et al (2013) Optimized chemical probes for REV-ERBα. J Med Chem 56:4729–4737. https://doi.org/10.1021/jm400458q
Solt LA et al (2012) Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature 485:62–68
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
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
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
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
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
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
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
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
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
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
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
Lamia KA et al (2011) Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature 480:552–556. https://doi.org/10.1038/nature10700
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
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
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
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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
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