{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:53:49Z","timestamp":1791557629091,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100608"],"award-info":[{"award-number":["82100608"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430022"],"award-info":[{"award-number":["82430022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2507500"],"award-info":[{"award-number":["2023YFC2507500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2013associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder, with few optimal pharmacotherapies. Ongoing studies are providing evidence that histone acetylation contributes to the progression of MASLD. This study investigated the alterations of specific histone acetylation sites in MASLD tissues and the effects of B029\u20102, a small\u2010molecule inhibitor targeting p300\/CBP acetylation activity, in mouse models of progressive fatty liver disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The acetylation of H3K27\/H3K18\/H3K9 was assessed in liver samples from MASLD patients and mice. The effect of the B029\u20102 in MASLD was assessed in MASLD models. A ChIP assay was conducted to investigate the epigenetic regulatory mechanism of ACSL4. Hepatic\u2010specific Acsl4\u2010knockout and overexpression mice were generated to validate the role of ACSL4 in MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observed a significant increase in p300 HAT activity, p300\/CBP\u2010induced H3K18ac and H3K27ac levels in MASLD and B029\u20102 markedly reduced hepatic steatosis in\u00a0vitro and in\u00a0vivo. Transcriptome analysis revealed that B029\u20102 inhibited the expression of genes in the triglyceride biosynthetic process and long\u2010chain fatty\u2010acyl\u2010CoA biosynthetic process. ChIP assay showed that H3K18ac, H3K27ac and p300 bind to the promoter region of\n                      <jats:italic>ACSL4<\/jats:italic>\n                      , and their binding is reduced by B029\u20102 treatment. AAV\u2010mediated hepatic\u2010specific overexpression of Acsl4 attenuated the effect of B029\u20102 on MASLD in mice, while hepatic\u2010specific Acsl4\u2010deficient in mice blocked the effect of B029\u20102.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>p300\/CBP\u2010mediated H3K18ac and H3K27ac regulate ACSL4\u2010dependent lipid biosynthesis in MASLD and might be a potential therapeutic target for the treatment of MASLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70846","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T08:06:06Z","timestamp":1788595566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Acetylation Activity of p300\/\n                    <scp>CBP<\/scp>\n                    Ameliorates Hepatic Steatosis Through Downregulation of\n                    <scp>ACSL4<\/scp>"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9859-9095","authenticated-orcid":false,"given":"Ling\u2010Yan","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Ping","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Han","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Hong","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-6614","authenticated-orcid":false,"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Changzheng Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7562-9909","authenticated-orcid":false,"given":"Xin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7137-112X","authenticated-orcid":false,"given":"Wei\u2010Fen","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"},{"name":"Department of Gastroenterology Changzheng Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.04.031"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-024-10774-3"},{"key":"e_1_2_11_4_1","first-page":"418","article-title":"Guidelines for the Prevention and Treatment of Metabolic Dysfunction\u2010Associated (Non\u2010Alcoholic) Fatty Liver Disease (Version 2024)","volume":"32","author":"Chinese Society of Hepatology, Chinese Medical Association","year":"2024","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2023.0485"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03018-2"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2413258"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01071-5"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.12.094"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.104996"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.318"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.3c05010"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41624"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.155953"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32148"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000684"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-1323"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03974-6"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.08.027"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2020.114067"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85963"},{"key":"e_1_2_11_22_1","article-title":"Aberrant Gene Expression Induced by a High Fat Diet Is Linked to H3K9 Acetylation in the Promoter\u2010Proximal Region","volume":"1864","author":"Morral N.","year":"2021","journal-title":"BBA\u2010Gene Regulatory Mechanisms"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16252"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2022-0362"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.750620"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.18079"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.01.014"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.122978"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.09.009"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2023.115935"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.10.270"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2024.124590"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2023.133151"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2408049121"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70846","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.70846","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70846","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:40:20Z","timestamp":1791556820000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,5]]},"references-count":33,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/liv.70846"],"URL":"https:\/\/doi.org\/10.1111\/liv.70846","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,5]]},"assertion":[{"value":"2025-09-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70846"}}