{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:20:47Z","timestamp":1783704047111,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2101001"],"award-info":[{"award-number":["2021YFC2101001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY18H070004"],"award-info":[{"award-number":["LY18H070004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LZ24H310002"],"award-info":[{"award-number":["LZ24H310002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Hepatic lipid deposition is a key factor in the development of NAFLD. <jats:italic>N<\/jats:italic><jats:sup>6<\/jats:sup>\u2010methyladenosine (m<jats:sup>6<\/jats:sup>A) modification, the most prevalent mRNA modification in eukaryotic cells, plays an important role in regulating hepatic lipid metabolism. However, its potential role in hepatic lipid deposition remains poorly understood. Histological and immunohistochemistry studies were used to investigate lipid deposition in free fatty acids (FFAs)\u2010incubated LO2 cells, high\u2010fat diet\u2010fed mice models and clinical samples. Stable overexpression and knockdown of AlkB homolog 5 (ALKBH5) was manipulated to investigate the effects of ALKBH5 on m<jats:sup>6<\/jats:sup>A methylation and lipid metabolism in hepatocytes. RNA\u2010sequencing transcriptome analysis and methylated RNA immunoprecipitation\u2010quantitative\u2010PCR analysis were used to reveal the potential downstream molecular targets of ALKBH5. ALKBH5 was down\u2010regulated in fatty liver compared to normal liver in both humans and mice. Overexpression of ALKBH5 significantly improved FFA\u2010induced lipid accumulation and promoted autophagosome\u2010lysosome fusion in hepatocytes. Meanwhile, knockdown of ALKBH5 significantly increased the expression of microtubule\u2010associated protein 1A\/1B\u2010light chain 3B and Sequestosome 1, leading to impaired autophagic flux and further lipid deposition in hepatocytes under FFA incubation. Overexpression of vacuolar protein sorting 11 (VPS11) reversed FFA\u2010induced lipid accumulation in ALKBH5\u2010silenced hepatocytes. Mechanistically, ALKBH5 alleviated hepatic lipid deposition and impaired autophagic flux by removing the m<jats:sup>6<\/jats:sup>A modification on <jats:italic>VPS11<\/jats:italic> mRNA to promote its translation. Collectively, our findings revealed an epigenetic mechanism by which ALKBH5 alleviates hepatic lipid deposition by restoring VPS11\u2010dependent autophagic flux, providing a potential target to counteract NAFLD.<\/jats:p>","DOI":"10.1111\/febs.17299","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T05:45:28Z","timestamp":1729575928000},"page":"5256-5275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The deficiency of <scp>ALKBH<\/scp>5 contributes to hepatic lipid deposition by impairing <scp>VPS<\/scp>11\u2010dependent autophagic flux"],"prefix":"10.1111","volume":"291","author":[{"given":"Linghuan","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou China"},{"name":"College of Chemistry and Materials Science Zhejiang Normal University  Jinhua China"},{"name":"Key Laboratory of the Ministry of Education for Advanced Catalysis Materials Zhejiang Normal University  Jinhua China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhai","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingqin","family":"Li","sequence":"additional","affiliation":[{"name":"Taizhou Municipal Hospital Taizhou University  Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanfang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zha","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengjiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3873-4061","authenticated-orcid":false,"given":"Hanbing","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31150"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30251"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32511-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.045"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2019-0009"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2020.06.003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.068"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.08.018"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.09.016"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.04.009"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11490"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2022.116323"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2021.100973"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.01.026"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2284-8"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41389-018-0054-6"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1720431"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1586246"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01059-0"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-023-00288-0"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105484"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2020.1736042"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.10.015"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.174900"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106608"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.77441"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.04.032"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1159-2"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.07.021"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2254191"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2718"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.412569"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26021"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005848"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31220"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.973116"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.577460"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1303-7"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02538-4"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2023.131354"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32963-0"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2146890"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810465"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.12565"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.17299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T11:19:14Z","timestamp":1733311154000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.17299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,21]]},"references-count":44,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/febs.17299"],"URL":"https:\/\/doi.org\/10.1111\/febs.17299","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,21]]},"assertion":[{"value":"2024-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}