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Cited by 54Circadian rhythm and melatoninSirtuins and Resveratrol in MedicineDietary Effects on Health

Nuclear receptor REVERBα is a state-dependent regulator of liver energy metabolism

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Hunter, A. Louise, Pelekanou, Charlotte E., Adamson, Antony, Downton, Polly, Barron, Nichola J., Cornfield, Thomas, Poolman, Toryn M., Humphreys, Neil +6 more·2020·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2005330117PMC PMC7568238
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Abstract

Significance: The circadian clock protein REVERBα is proposed to be a key regulator of liver metabolism. We now show that REVERBα action is critically dependent on metabolic state. Using transgenic mouse models, we show that the true role of REVERBα is to buffer against aberrant responses to metabolic perturbation, rather than confer rhythmic regulation to programs of lipid synthesis and storage, as has been thought previously. Thus, in the case of liver metabolism, the clock does not so much drive rhythmic processes, as provide protection against mistimed feeding cues. Understanding how the clock is coupled to metabolism is critical for understanding metabolic disease and the impacts of circadian disruptors such as shift work and 24-h lifestyles.

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  • Transcription factor activities may only be fully revealed in non-basal conditions and transcription factors may be important to (re-)establish rather than to maintain cell-specific transcriptomes.

    “Recent studies have found that TF activities may only be fully revealed in non‐basal conditions and that TFs may be important to (re‐)establish rather than to maintain cell‐specific transcriptomes (Hunter et al, 2020; Lo et al, 2022).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Hunter et al, 2020

    The Discussion says that a wider program of REVERBα-regulated genes is unmasked by metabolic perturbation, supporting the point that transcription-factor activity may be more apparent in non-basal conditions. It does not address whether transcription factors re-establish, rather than maintain, cell-specific transcriptomes; searches for that distinction found no supporting passage. (LLM, conf=0.86)

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Cited by

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Authors
Hunter, A. L., Pelekanou, C. E., Adamson, A., Downton, P., Barron, N. J., Cornfield, T., Poolman, T. M., Humphreys, N., Cunningham, P. S., Hodson, L., Loudon, A. S. I., Iqbal, M., Bechtold, D. A., & Ray, D. W.
Affiliations
  • Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT Manchester, United Kingdom;
  • University of Manchester (GB)
  • John Radcliffe Hospital (GB)
Corresponding author
  • Bechtold, David A.
  • Ray, David W.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2020-09-28
Volume
117
Issue
41
Pages
25869-25879
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2005330117
PMC
PMC7568238
OpenAlex
W3090234017
Cited by
54
References
6
Citations by year
2026: 8 · 2025: 6 · 2024: 9 · 2023: 7 · 2022: 12 · 2021: 9 · 2020: 2
FWCI
3.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • RCUK | Medical Research Council (MR/N021479/1, MR/P00279X/1, MR/P011853/1, MR/P023576/1)
  • RCUK | Biotechnology and Biological Sciences Research Council (BB/IO18654/1)
  • Wellcome (107849/Z/15/Z)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
Keywords
NR1D1, nuclear receptors, circadian clock, liver energy metabolism, metabolic status, lipogenesis, fat deposition, feeding cues, circadian rhythm disruption, shift work, metabolic disorders
MeSH terms
Animals, Energy Metabolism, Gene Expression Regulation, Liver, Male, Mice, Inbred C57BL, Mice, Knockout, Amino Acid Motifs, Mice, CLOCK Proteins, Nuclear Receptor Subfamily 1, Group D, Member 1, Circadian Clocks

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