Evidence map›Paper›PMID 40760448›Full record

ArticleClinical epigenetics2025

Gradual DNA methylation changes reveal transcription factors implicated in metabolic dysfunction-associated steatotic liver disease progression and epigenetic age acceleration.

Evelien Van Dijck, Steven Van Laere, Emilie Logie, Steven Timmermans, Erik Fransen, Joe Ibrahim, Timothy J Kendall, Jonathan A Fallowfield, Ligia M Mateiu, Claude Libert and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
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

16 authors.

Evelien Van DijckCell Death Signaling-Epigenetics Lab, Department Biomedical Sciences, University of Antwerp, 2610, Wilrijk, Belgium. evelien.vandijck@uantwerpen.be.
Steven Van LaereCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, Wilrijk, Belgium.
Emilie LogieCell Death Signaling-Epigenetics Lab, Department Biomedical Sciences, University of Antwerp, 2610, Wilrijk, Belgium.
Steven TimmermansCenter for Inflammation Research, Vlaams Instituut Voor Biotechnologie (VIB), Ghent, Belgium.
Erik FransenCentre of Medical Genetics, University of Antwerp, 2650, Edegem, Belgium.
Joe IbrahimCentre of Medical Genetics, University of Antwerp, 2650, Edegem, Belgium.
Timothy J KendallCentre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
Jonathan A FallowfieldCentre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
Ligia M MateiuCentre of Medical Genetics, University of Antwerp, 2650, Edegem, Belgium.
Claude LibertCenter for Inflammation Research, Vlaams Instituut Voor Biotechnologie (VIB), Ghent, Belgium.
Guy Van CampCentre of Medical Genetics, University of Antwerp, 2650, Edegem, Belgium.
An VerrijkenDepartment of Endocrinology, Diabetology and Metabolic Diseases, Antwerp University Hospital, 2650, Edegem, Belgium.
Luc Van GaalDepartment of Endocrinology, Diabetology and Metabolic Diseases, Antwerp University Hospital, 2650, Edegem, Belgium.
Sven FrancqueDepartment of Gastroenterology and Hepatology, Antwerp University Hospital, 2650, Edegem, Belgium.
Wim Van HulCentre of Medical Genetics, University of Antwerp, 2650, Edegem, Belgium.
Wim Vanden BergheCell Death Signaling-Epigenetics Lab, Department Biomedical Sciences, University of Antwerp, 2610, Wilrijk, Belgium. wim.vandenberghe@uantwerpen.be.

Funding

European Commission projects HEPADIP LSHM-CT-2005-018734Fonds Wetenschappelijk Onderzoek 11E6921NFonds Wetenschappelijk Onderzoek 1802154NFonds Wetenschappelijk Onderzoek G1179120NGeconcerteerde Onderzoeksactie (GOA) FFB180348Innovate UK TS/R017581/1Methusalem OEC grant - "GENOMED" FFB190208RESOLVE FP7-305707
6 · The paper itself

Abstract

backgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, but its pathophysiological mechanisms remain elusive. It is a progressive disease, encompassing hepatic steatosis, steatohepatitis with (out) fibrosis, and ultimately cirrhosis and hepatocellular carcinoma. DNA methylation (DNAm) is dysregulated in MASLD and may play a central role in its pathogenesis. Additionally, aging is associated with MASLD and shares common processes of chronic inflammation and oxidative stress. Therefore, this study focuses on DNAm changes in relation to MASLD progression and epigenetic age acceleration (EAA).

resultsLiver biopsies from 22 individuals with varying MASLD status were analyzed using Infinium MethylationEPIC BeadChip arrays. Strikingly, progression of MASLD was characterized by gradual DNAm changes, revealing multiple associated KEGG pathways. Additionally, Horvath's EAA significantly correlated with MASLD stage and individual histological MASLD parameters while LiverClock's EAA correlated only with MASLD stage. In contrast, both Horvath's intrinsic EAA and HepClock's EAA showed no significant correlations. Integrative analyses, leveraging both gradual MASLD and Horvath's EAA DNAm signatures, gene expression (n = 118), and a MASLD-specific transcriptional regulatory network, identified (regulon-specific) transcription factors implicated in MASLD and EAA progression, representing a transcription factor-network of redox (ferroptosis), immune, and metabolic/endocrine related epigenetic processes.

conclusionGradual DNAm changes were found to align with progression of MASLD and EAA, with EAA a potential nonbiased quantitative biomarker for MASLD. Integrative analysis highlighted potential new therapeutic transcription factor targets, with special emphasis on AEBP1 and emerging nuclear receptors including CAR(NR1I3), MR(NR3C2), GR(NR3C1), and ESRRG, underscoring the potential of epigenetic redox-metabolic therapies for MASLD.

Indexed as

DNA MethylationEpigenesis, GeneticFatty LiverTranscription FactorsAdultAgedDisease ProgressionFemaleHumansLiverMaleMiddle AgedNon-alcoholic Fatty Liver DiseaseTranscription FactorsDNA methylationEpigenetic ageEpigenetic age accelerationEpigeneticsImmune systemMASLDMetabolismNetwork analysisRedoxTranscription factor

Identifiers

PMID40760448
PMCPMC12323057

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.