Evidence map›Paper›PMID 35739588›Full record

ArticleGenome medicine2022

Acetyl-CoA metabolism drives epigenome change and contributes to carcinogenesis risk in fatty liver disease.

Gabriella Assante, Sriram Chandrasekaran, Stanley Ng, Aikaterini Tourna, Carolina H Chung, Kowsar A Isse, Jasmine L Banks, Ugo Soffientini, Celine Filippi, Anil Dhawan and 9 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% of its field
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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Inhibition of Acetylation Activity of p300/CBP Ameliorates Hepatic Steatosis Through Downregulation of ACSL4.Liver international : official journal of the International Association for the Study of the Liver · 2026
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  6. Crosstalk BetweenCancers · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 9 institutions in 4 countries.

Gabriella AssanteInstitute of Hepatology, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK.
Sriram ChandrasekaranProgram in Chemical Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Stanley NgWellcome Trust Sanger Institute, Cambridge, UK.
Aikaterini TournaInstitute of Hepatology, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK.
Carolina H ChungDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
Kowsar A IsseInstitute of Hepatology, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK.
Jasmine L BanksUNSW Sydney, Sydney, Australia.
Ugo SoffientiniInstitute of Hepatology, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK.
Celine FilippiInstitute of Liver Studies, King's College Hospital, London, UK.
Anil DhawanInstitute of Liver Studies, King's College Hospital, London, UK.
Mo LiuProgramme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore.
Steven G RozenProgramme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore.
Matthew HoareCRUK Cambridge Institute, Cambridge, UK.
Peter CampbellWellcome Trust Sanger Institute, Cambridge, UK.
J William O BallardDepartment of Ecology, Environment and Evolution, La Trobe University, Bundoora, Melbourne, VIC, 3086, Australia.
Nigel TurnerUNSW Sydney, Sydney, Australia.
Margaret J MorrisUNSW Sydney, Sydney, Australia.
Shilpa ChokshiInstitute of Hepatology, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK.
Neil A YoungsonInstitute of Hepatology, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK. n.youngson@researchinliver.org.uk.
Foundation for Liver Research · GBUNSW Sydney · AUDuke-NUS Medical School · SGKing's College Hospital · GBUniversity of Michigan–Ann Arbor · USWellcome Sanger Institute · GBAddenbrooke's Hospital · GBKing's College London · GBLa Trobe University · AU

Funding

Linking metabolic activity with drug sensitivity using metabolic influence networksR35GM137795 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Chandrasekaran · 2020 to 2026
$2.6M
National Institute of Health (US) R35 GM13779501
6 · The paper itself

Abstract

backgroundThe incidence of non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is increasing worldwide, but the steps in precancerous hepatocytes which lead to HCC driver mutations are not well understood. Here we provide evidence that metabolically driven histone hyperacetylation in steatotic hepatocytes can increase DNA damage to initiate carcinogenesis.

methodsGlobal epigenetic state was assessed in liver samples from high-fat diet or high-fructose diet rodent models, as well as in cultured immortalized human hepatocytes (IHH cells). The mechanisms linking steatosis, histone acetylation and DNA damage were investigated by computational metabolic modelling as well as through manipulation of IHH cells with metabolic and epigenetic inhibitors. Chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) and transcriptome (RNA-seq) analyses were performed on IHH cells. Mutation locations and patterns were compared between the IHH cell model and genome sequence data from preneoplastic fatty liver samples from patients with alcohol-related liver disease and NAFLD.

resultsGenome-wide histone acetylation was increased in steatotic livers of rodents fed high-fructose or high-fat diet. In vitro, steatosis relaxed chromatin and increased DNA damage marker γH2AX, which was reversed by inhibiting acetyl-CoA production. Steatosis-associated acetylation and γH2AX were enriched at gene clusters in telomere-proximal regions which contained HCC tumour suppressors in hepatocytes and human fatty livers. Regions of metabolically driven epigenetic change also had increased levels of DNA mutation in non-cancerous tissue from NAFLD and alcohol-related liver disease patients. Finally, genome-scale network modelling indicated that redox balance could be a key contributor to this mechanism.

conclusionsAbnormal histone hyperacetylation facilitates DNA damage in steatotic hepatocytes and is a potential initiating event in hepatocellular carcinogenesis.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsNon-alcoholic Fatty Liver DiseaseAcetyl Coenzyme AAnimalsCarcinogenesisDiet, High-FatEpigenomeFructoseHistonesHumansLiverMiceMice, Inbred C57BLAcetyl Coenzyme AFructoseHistonesARLDHepatocellular carcinomaHistone acetylationNAFLDSteatosisTelomerase

Identifiers

PMID35739588
PMCPMC9219160
OpenAlexW4283318751

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.