{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:09:39Z","timestamp":1788883779287,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Steatosis is the early pathological change in alcohol\u2010associated liver disease. However, its precise mechanism is still unclear. The present study is aimed to explore the role and mechanism of acetyl\u2010CoA synthetase 2 (ACSS2) in acute alcohol\u2010induced lipogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The increase in ACSS2 nuclear import and histone H3 acetylation were observed in mice after intraperitoneally injected with 2 g\/kg ethanol or oral administration of 5\u2009g\/kg ethanol and also validated in hepatocytes stimulated with ethanol or acetate. The role of ACSS2 was further explored in liver\u2010specific ACSS2 knockdown mice fed with ethanol\u2010containing diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alcohol challenge induced hepatic lipid deposition and upregulated lipogenic genes in mice. It also promoted ACSS2 nuclear import and increased histone H3 acetylation. In hepatocytes, ethanol induced similar phenomena whereas ACSS2 knockdown blocked histone acetylation and lipogenic gene induction. P300\/CBP associated factor (PCAF), but not general control nonderepressible 5, CREB\u2010binding protein (CBP) and p300, facilitated H3K9 acetylation responding to ethanol challenge. CUT&amp;RUN assay showed the enrichment of acetylated histone H3K9 surrounding <jats:italic>Fasn<\/jats:italic> and <jats:italic>Acaca<\/jats:italic> promoters. These results indicated that ethanol metabolism promoted ACSS2 nuclear import to support lipogenesis via H3K9 acetylation. In alcohol\u2010feeding mice, liver\u2010specific ACSS2 knockdown blocked the interaction between PCAF and H3K9 and suppressed lipogenic gene induction in the liver, demonstrating the critical role of ACSS2 in lipogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that alcohol metabolism generated acetyl\u2010CoA in the nucleus dependently on nuclear ACSS2, contributing to epigenetic regulation of lipogenesis in hepatic steatosis. Targeting ACSS2 may be a potential therapeutical strategy for acute alcoholic liver steatosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15600","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T07:26:20Z","timestamp":1684135580000},"page":"1729-1740","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Inhibition of <scp>ACSS2<\/scp> attenuates alcoholic liver steatosis via epigenetically regulating de novo lipogenesis"],"prefix":"10.1111","volume":"43","author":[{"given":"Yawen","family":"Lu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-4447","authenticated-orcid":false,"given":"Yimeng","family":"Chen","sequence":"additional","affiliation":[{"name":"State 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