A cell-autonomous mammalian 12 hr clock coordinates metabolic and stress rhythms
Open accessAbstract
Besides circadian rhythms, oscillations cycling with a 12 hr period exist. However, the prevalence, origin, regulation, and function of mammalian 12 hr rhythms remain elusive. Utilizing an unbiased mathematical approach identifying all superimposed oscillations, we uncovered prevalent 12 hr gene expression and metabolic rhythms in mouse liver, coupled with a physiological 12 hr unfolded protein response oscillation. The mammalian 12 hr rhythm is cell autonomous, driven by a dedicated 12 hr pacemaker distinct from the circadian clock, and can be entrained in vitro by metabolic and ER stress cues. Mechanistically, we identified XBP1s as a transcriptional regulator of the mammalian 12 hr clock. Downregulation of the 12 hr gene expression strongly correlates with human hepatic steatosis and steatohepatitis, implying its importance in maintaining metabolic homeostasis. The mammalian 12 hr rhythm of gene expression also is conserved in nematodes and crustaceans, indicating an ancient origin of the 12 hr clock. Our work sheds new light on how perturbed biological rhythms contribute to human disease.
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A 12-h rhythm, reminiscent of circatidal oscillations, has been found in transcriptional dynamics of mouse liver.
“Although a direct connection with the lunar cycle is still elusive, it is interesting to note that a 12-h rhythm, reminiscent of circatidal oscillations, has been also found in transcriptional dynamics of mouse liver [134].”
From The Still Dark Side of the Moon: Molecular Mechanisms of Lunar-Controlled Rhythms and Clocks (2020) · cites this paper as [134]
XBP1 is required for the maintenance of the 12-h rhythmicity in mouse liver.
“XBP1 (an unfolded protein response transcription factor) is required for the maintenance of this rhythmicity.”
From The Still Dark Side of the Moon: Molecular Mechanisms of Lunar-Controlled Rhythms and Clocks (2020) · cites this paper as [134]
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References 46 · Cited by 146
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- Taruskin R 2008 Music in the Western World: A History in Documents (2d ed.) Choral Journal 48 68 70
- Authors
- Zhu, B., Zhang, Q., Pan, Y., Mace, E. M., York, B., Antoulas, A. C., Dacso, C. C., & O’Malley, B. W.
- Affiliations
- Baylor College of Medicine (US)
- Rice University (US)
- University of Houston (US)
- Corresponding author
- O’Malley, Bert W.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 25
- Issue
- 6
- Pages
- 1305-1319.e9
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5526350
- OpenAlex
- W2624131315
- Cited by
- 146
- References
- 46
- Citations by year
- 2026: 15 · 2025: 10 · 2024: 28 · 2023: 16 · 2022: 17 · 2021: 11 · 2020: 13 · 2019: 15 · 2018: 16 · 2017: 5
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- NIH (U24 DK097748, R01 HD07857)
- Brockman Medical Research Foundation
- Center for Advancement of Science in Space
- Peter J. Fluor Family Fund
- Philip J. Carroll, Jr., Professorship
- Joyce Family Foundation
- NSF (CCF-1320866)
- DFG (AN-693/1-1)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- circadian rhythm, unfolded protein response, XBP1, endoplasmic reticulum stress, metabolic rhythms, hepatic steatosis, steatohepatitis
- MeSH terms
- X-Box Binding Protein 1, Animals, Cell Line, Gene Expression Regulation, Humans, Mice, Transgenic, Mice, Unfolded Protein Response, Circadian Clocks, Endoplasmic Reticulum Stress
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