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Cited by 246Circadian rhythm and melatoninLiver physiology and pathologySleep and Work-Related Fatigue

The circadian clock and liver function in health and disease

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Mukherji, Atish, Bailey, Shannon M., Staels, Bart, Baumert, Thomas F.·2019·Journal of Hepatology
DOI 10.1016/j.jhep.2019.03.020PMC PMC7613420
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Abstract

Each day, all organisms are subjected to changes in light intensity because of the Earth's rotation around its own axis. To anticipate this geo-physical variability, and to appropriately respond biochemically, most species, including mammals, have evolved an approximate 24-hour endogenous timing mechanism known as the circadian clock (CC). The 'clock' is self-sustained, cell autonomous and present in every cell type. At the core of the clock resides the CC-oscillator, an exquisitely crafted transcriptional-translational feedback system. Remarkably, components of the CC-oscillator not only maintain daily rhythmicity of their own synthesis, but also generate temporal variability in the expression levels of numerous target genes through transcriptional, post-transcriptional and post-translational mechanisms, thus, ensuring proper chronological coordination in the functioning of cells, tissues and organs, including the liver. Indeed, a variety of physiologically critical hepatic functions and cellular processes are CC-controlled. Thus, it is not surprising that modern lifestyle factors (e.g. travel and jet lag, night and rotating shift work), which force 'circadian misalignment', have emerged as major contributors to global health problems including obesity, non-alcoholic fatty liver disease and steatohepatitis. Herein, we provide an overview of the CC-dependent pathways which play critical roles in mediating several hepatic functions under physiological conditions, and whose deregulation is implicated in chronic liver diseases including non-alcoholic steatohepatitis and alcohol-related liver disease.

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  • Several Hep-IDCONNECT transcription factors are central to establishment of rhythmic hepatocyte gene expression, including both circadian (BHLHE40, CLOCK, DBP, NFIL3, NR1D1/2) and ultradian (XBP1) rhythms.

    “Several Hep‐IDCONNECT TFs are central to establishment of rhythmic hepatocyte gene expression (Appendix Fig S11) including both circadian (BHLHE40, CLOCK, DBP, NFIL3, NR1D1/2; Mukherji et al, 2019) and ultradian (XBP1; Meng et al, 2020; Pan et al, 2020) rhythms.”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Mukherji et al, 2019

    The Introduction sections on the mammalian circadian-clock system and hepatic functions describe CLOCK, DBP, E4BP4, and REV-ERBα/β in circadian regulation of gene expression, including in the liver. Our copy does not identify BHLHE40 or explicitly connect the name NFIL3 to E4BP4, so it does not substantiate the entire cited list. The XBP1 ultradian claim has separate citations in the printed sentence and is not attributed to Mukherji et al. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Rhythmic and zonated hepatic gene expression are crucial to maintain appropriate liver metabolic and non-metabolic activities.

    “rhythmic and zonated hepatic gene expression are crucial to maintain appropriate liver metabolic and non‐metabolic activities (Mukherji et al, 2019; Meng et al, 2020; Pan et al, 2020; Paris & Henderson, 2022).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Mukherji et al, 2019

    The Introduction’s “Circadian regulation of hepatic functions” section links rhythmic gene expression to liver physiology, including metabolic processes and DNA repair. The “Chronopharmacology” section also describes rhythmic expression of detoxification genes. The passages do not address zonated hepatic gene expression, so that part of the claim is unsupported by this source. (LLM, conf=0.88)

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Authors
Mukherji, A., Bailey, S. M., Staels, B., & Baumert, T. F.
Affiliations
  • Inserm (FR)
  • University of Alabama at Birmingham (US)
Corresponding author
  • Mukherji, Atish
  • Baumert, Thomas F.
ORCID
Venue
Journal of Hepatology
Publisher
Elsevier BV
Published
2019-07
Volume
71
Issue
1
Pages
200-211
ISSN
0168-8278 (ISSN-L)
DOI
10.1016/j.jhep.2019.03.020
PMC
PMC7613420
OpenAlex
W2933956188
Cited by
246
References
25
Citations by year
2026: 32 · 2025: 37 · 2024: 41 · 2023: 36 · 2022: 41 · 2021: 28 · 2020: 24 · 2019: 5
FWCI
3.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Hepatology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, cc-by)
Funders
  • NIAID (1R03AI131066-01A1, NCI R21 CA209940)
  • Fondation ARC pour la Recherche sur le Cancer (IHU201301187)
  • ERC (694717, 671231)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Keywords
circadian clock, liver function, transcription-translation feedback loop, circadian misalignment, shift work, jet lag, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity, alcoholic liver disease
MeSH terms
Circadian Rhythm, Humans, Liver, Liver Diseases, Circadian Clocks

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