Evidence map›Paper›PMID 42119922›Full record

ArticleCellular and molecular gastroenterology and hepatology2026

Hepatocyte Circadian Clocks Control Cholesterol Metabolism and Protect From Metabolic Dysfunction-Associated Steatohepatitis.

Leonardo V M de Assis, Lina Jegodzinski, Julica Inderhees, Sylvia J Wowro, Juliana Marques Affonso, Isabel Heyde, Emelie Luise Fischer, Witigo von Schönfels, Andrea Schenk, Florian Roßner and 4 more

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Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Leonardo V M de AssisInstitute of Neurobiology, Center of Brain Behavior and Metabolism, University of Lübeck, Lübeck, Germany; University Hospital Schleswig-Holstein, Lübeck, Germany; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: leonardo.deassis@cmb.gu.se.
Lina JegodzinskiDepartment of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany.
Julica InderheesBioanalytic Core Facility, Center of Brain Behavior and Metabolism, University of Lübeck, Lübeck, Germany.
Sylvia J WowroCharité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Pharmacology, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Berlin, Germany.
Juliana Marques AffonsoDepartment of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany.
Isabel HeydeInstitute of Neurobiology, Center of Brain Behavior and Metabolism, University of Lübeck, Lübeck, Germany.
Emelie Luise FischerInstitute of Neurobiology, Center of Brain Behavior and Metabolism, University of Lübeck, Lübeck, Germany.
Witigo von SchönfelsDepartment of General, Visceral, Thoracic, Transplantation, and Pediatric Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany.
Andrea SchenkDepartment of Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany.
Florian RoßnerInstitute of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Michael SchuppCharité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Pharmacology, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Berlin, Germany.
Jens U MarquardtDepartment of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany.
Münevver DemirDepartment of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany.
Henrik OsterInstitute of Neurobiology, Center of Brain Behavior and Metabolism, University of Lübeck, Lübeck, Germany; University Hospital Schleswig-Holstein, Lübeck, Germany. Electronic address: henrik.oster@uni-luebeck.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsThe circadian clock synchronizes physiological processes with the 24-hour light-dark cycle. Clock disruption contributes to metabolic disorders, including metabolic dysfunction-associated steatohepatitis.

methodsWe investigated the role of the hepatocyte clock in metabolic dysfunction-associated steatohepatitis using hepatocyte-specific Bmal1 deletion (Hep-Bmal1KO) mice.

resultsHep-Bmal1KO mice showed faster metabolic dysfunction-associated steatohepatitis progression with increased hepatic cholesterol, inflammation, and fibrosis. Transcriptomic and lipidomic analyses revealed dysregulated cholesterol metabolism in Hep-Bmal1KO mice, marked by reduced expression and disrupted rhythmicity of key cholesterol-related genes. Bioinformatic analyses identified Chrebp as a potential coregulator of these transcriptional changes. In an in vitro model with palmitate exposure and gene silencing, we found that Bmal1, but not Chrebp, regulated cholesterol accumulation, indicating Bmal1's specific role in hepatic cholesterol metabolism. Translating our findings to a human patient cohort revealed a significantly shifted circadian phase, despite no marked effect on hepatic cholesterol levels in the livers of patients with more advanced liver disease (ie, metabolic dysfunction-associated steatohepatitis) compared with simple steatosis.

conclusionsTaken altogether, our findings offer a roadmap to understand the hepatocyte clock's role in metabolic dysfunction-associated steatohepatitis and its potential as a therapeutic target.

Indexed as

ARNTL Transcription FactorsCholesterolCircadian ClocksFatty LiverHepatocytesAnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCircadian RhythmDisease Models, AnimalHumansLipid MetabolismLiverMaleMiceMice, KnockoutTranscription FactorsARNTL Transcription FactorsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBmal1 protein, mouseCholesterolMlxipl protein, mouseTranscription FactorsBioinformaticsBmal1ChrebpCircadian BioinformaticsClock GenesLipid MetabolismLiver MetabolismPalmitate

Identifiers

PMID42119922
PMCPMC13316630

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.