{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:35:00Z","timestamp":1792773300682,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"59","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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":["82370904 82470933 82270942"],"award-info":[{"award-number":["82370904 82470933 82270942"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intermittent fasting (IF) ameliorates metabolic dysfunction\u2010associated steatotic liver disease (MASLD), but the underlying mechanism remains unclear. Combined CUT&amp;Run and transcriptomic analysis shows that hepatic Ahcy is controlled by the super\u2011enhancer (SE) and acts as a key mediator of IF's benefit. Liver\u2011specific Ahcy knockout worsens high\u2011fat diet (HFD)\u2011induced hepatic steatosis and blunts the protective effect of IF. Furthermore, inhibition of Brd4 or deletion of the core SE region reduces Ahcy expression and exacerbates lipid accumulation in vivo or in vitro. Hnf4a is identified as the transcription factor driving the Ahcy\u2010SE. In vitro and in vivo experiments demonstrate that IF\u2010activated Hnf4a directly binds to and activates the Ahcy\u2010SE. Ahcy knockdown attenuates the lipid\u2010deposition\u2010reducing effect of Hnf4a overexpression in mice fed a HFD. In Ahcy\n                    <jats:sup>LKO<\/jats:sup>\n                    mice, the liver SAM\/SAH ratio is reduced, and Reduced Representation Bisulfite Sequencing (RRBS) and transcriptome sequencing reveal liver\u2010specific methylation remodeling. One manifestation of this remodeling is hypermethylation of metabolic gene promoters, including the Acot12 promoter, where aberrant recruitment of Dnmt3b leads to silencing of the gene and impaired lipid hydrolysis. Therefore, these findings define an IF\u2010Hnf4a\u2010Ahcy pathway that activates SE\u2010driven Ahcy to orchestrate protective epigenetic reprogramming in MASLD.\n                  <\/jats:p>","DOI":"10.1002\/advs.76826","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:14:41Z","timestamp":1785154481000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ahcy Acts as an Effector of Hnf4a\u2010Driven Super\u2010Enhancer Activation to Alleviate MASLD During Intermittent Fasting"],"prefix":"10.1002","volume":"13","author":[{"given":"Huafeng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism The Eighth Affiliated Hospital Southern Medical University (The First People's Hospital of Shunde, Foshan)  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The Eighth Affiliated Hospital Southern Medical University (The First People's Hospital of Shunde, Foshan)  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Guangzhou First People's Hospital  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7549-8868","authenticated-orcid":false,"given":"Wenqiang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The Eighth Affiliated Hospital Southern Medical University (The First People's Hospital of Shunde, Foshan)  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1662-0971","authenticated-orcid":false,"given":"Fen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The Eighth Affiliated Hospital Southern Medical University (The First People's Hospital of Shunde, Foshan)  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5329-524X","authenticated-orcid":false,"given":"Hua","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The Eighth Affiliated Hospital Southern Medical University (The First People's Hospital of Shunde, Foshan)  Foshan Guangdong China"},{"name":"Medical Research Center The Eighth Affiliated Hospital Southern Medical University (The First People's Hospital of Shunde, Foshan)  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102023\u2010330595"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.04.014"},{"issue":"9","key":"e_1_2_9_4_1","first-page":"27","article-title":"Non\u2010Alcoholic Fatty Liver Disease in Elderly","author":"Krivosheev A. 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