Evidence map›Paper›PMID 39086681›Full record

ArticleFrontiers in molecular medicine2023

Loss of PPARα function promotes epigenetic dysregulation of lipid homeostasis driving ferroptosis and pyroptosis lipotoxicity in metabolic dysfunction associated Steatotic liver disease (MASLD).

Claudia Theys, Tineke Vanderhaeghen, Evelien Van Dijck, Cedric Peleman, Anne Scheepers, Joe Ibrahim, Ligia Mateiu, Steven Timmermans, Tom Vanden Berghe, Sven M Francque and 3 more

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Article in Frontiers in molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

  1. Ferroptosis in liver biology and diseases.Hepatology communications · 2026
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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

13 authors.

Claudia TheysProtein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Tineke VanderhaeghenCenter for Inflammation Research, VIB, Ghent, Belgium.
Evelien Van DijckCenter of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Cedric PelemanLaboratory of Experimental Medicine and Pediatrics, Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.
Anne ScheepersCenter of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Joe IbrahimCenter of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Ligia MateiuCenter of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Steven TimmermansCenter for Inflammation Research, VIB, Ghent, Belgium.
Tom Vanden BergheCenter for Inflammation Research, VIB, Ghent, Belgium.
Sven M FrancqueLaboratory of Experimental Medicine and Pediatrics, Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.
Wim Van HulCenter of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Claude LibertCenter for Inflammation Research, VIB, Ghent, Belgium.
Wim Vanden BergheProtein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is a growing epidemic with an estimated prevalence of 20%-30% in Europe and the most common cause of chronic liver disease worldwide. The onset and progression of MASLD are orchestrated by an interplay of the metabolic environment with genetic and epigenetic factors. Emerging evidence suggests altered DNA methylation pattern as a major determinant of MASLD pathogenesis coinciding with progressive DNA hypermethylation and gene silencing of the liver-specific nuclear receptor PPARα, a key regulator of lipid metabolism. To investigate how PPARα loss of function contributes to epigenetic dysregulation in MASLD pathology, we studied DNA methylation changes in liver biopsies of WT and hepatocyte-specific PPARα KO mice, following a 6-week CDAHFD (choline-deficient, L-amino acid-defined, high-fat diet) or chow diet. Interestingly, genetic loss of PPARα function in hepatocyte-specific KO mice could be phenocopied by a 6-week CDAHFD diet in WT mice which promotes epigenetic silencing of PPARα function via DNA hypermethylation, similar to MASLD pathology. Remarkably, genetic and lipid diet-induced loss of PPARα function triggers compensatory activation of multiple lipid sensing transcription factors and epigenetic writer-eraser-reader proteins, which promotes the epigenetic transition from lipid metabolic stress towards ferroptosis and pyroptosis lipid hepatoxicity pathways associated with advanced MASLD. In conclusion, we show that PPARα function is essential to support lipid homeostasis and to suppress the epigenetic progression of ferroptosis-pyroptosis lipid damage associated pathways towards MASLD fibrosis.

Indexed as

bile acid metabolismepigeneticsferroptosislipid metabolismMASLDNAFLDPPARαpyroptosis

Identifiers

PMID39086681
PMCPMC11285560

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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 OpenQuestion graph.