{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:26:35Z","timestamp":1789590395535,"version":"build-2803163510"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020595","name":"Taiwan Ministry of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007750","name":"National Cheng Kung University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007750","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["111-2320-B-006-033"],"award-info":[{"award-number":["111-2320-B-006-033"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Nutritional Biochemistry"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.jnutbio.2025.110227","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:48:42Z","timestamp":1765007322000},"page":"110227","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Promoter demethylation and protein O-GlcNAcylation-mediated enhancement of fatty acid synthase contributes to hepatic steatosis and inflammation in MASLD"],"prefix":"10.1016","volume":"150","author":[{"given":"Zou-Han","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-I","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Wei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9935-6853","authenticated-orcid":false,"given":"Zong-Chen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Ting","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hui","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-En","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Min","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-0884","authenticated-orcid":false,"given":"Chien-Chin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-500X","authenticated-orcid":false,"given":"I-Chen","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"16","key":"10.1016\/j.jnutbio.2025.110227_bib0001","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4254\/wjh.v9.i16.715","article-title":"Non-alcoholic fatty liver disease: an expanded review","volume":"9","author":"Benedict","year":"2017","journal-title":"World J Hepatol"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0002","doi-asserted-by":"crossref","DOI":"10.1016\/j.addr.2021.113869","article-title":"Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis","volume":"176","author":"Kumar","year":"2021","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0003","article-title":"Targeting mitochondrial ROS-mediated ferroptosis by quercetin alleviates high-fat diet-induced hepatic lipotoxicity","volume":"13","author":"Jiang","year":"2022","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0004","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/7514802","article-title":"Ginsenoside Rg1 ameliorates palmitic acid-induced hepatic steatosis and inflammation in HepG2 Cells via the AMPK\/NF-\u03baB pathway","volume":"2019","author":"Xiao","year":"2019","journal-title":"Int J Endocrinol"},{"issue":"9","key":"10.1016\/j.jnutbio.2025.110227_bib0005","doi-asserted-by":"crossref","first-page":"3898","DOI":"10.1039\/D0FO02736G","article-title":"Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K\/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD","volume":"12","author":"Li","year":"2021","journal-title":"Food Funct"},{"issue":"5","key":"10.1016\/j.jnutbio.2025.110227_bib0006","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI23621","article-title":"Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease","volume":"115","author":"Donnelly","year":"2005","journal-title":"J Clin Invest"},{"issue":"5","key":"10.1016\/j.jnutbio.2025.110227_bib0007","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1002\/hep.32045","article-title":"Fatty acid synthase-suppressor screening identifies sorting nexin 8 as a therapeutic target for NAFLD","volume":"74","author":"Hu","year":"2021","journal-title":"Hepatology"},{"issue":"3","key":"10.1016\/j.jnutbio.2025.110227_bib0008","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1053\/j.gastro.2013.11.049","article-title":"Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease","volume":"146","author":"Lambert","year":"2014","journal-title":"Gastroenterology"},{"issue":"5","key":"10.1016\/j.jnutbio.2025.110227_bib0009","first-page":"505","article-title":"Expression of fatty acid synthase in nonalcoholic fatty liver disease","volume":"3","author":"Dorn","year":"2010","journal-title":"Int J Clin Exp Pathol"},{"issue":"31","key":"10.1016\/j.jnutbio.2025.110227_bib0010","doi-asserted-by":"crossref","first-page":"11245","DOI":"10.1073\/pnas.0404297101","article-title":"Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver","volume":"101","author":"Chen","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"10.1016\/j.jnutbio.2025.110227_bib0011","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1172\/JCI128073","article-title":"Hepatic slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes","volume":"130","author":"Liu","year":"2020","journal-title":"J Clin Invest"},{"issue":"5","key":"10.1016\/j.jnutbio.2025.110227_bib0012","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.bbalip.2011.09.017","article-title":"Fatty acid synthase and liver triglyceride metabolism: housekeeper or messenger?","volume":"1821","author":"Jensen-Urstad","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0013","article-title":"An update in epigenetics in metabolic-associated fatty liver disease","volume":"8","author":"Rodriguez-Sanabria","year":"2021","journal-title":"Front Med (Lausanne)."},{"issue":"6","key":"10.1016\/j.jnutbio.2025.110227_bib0014","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.3390\/cells10061355","article-title":"Epigenetic regulation of peroxisome proliferator-activated receptor gamma mediates high-fat diet-induced non-alcoholic fatty liver disease","volume":"10","author":"Hajri","year":"2021","journal-title":"Cells"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0015","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.omto.2020.06.010","article-title":"Insulin and metformin control cell proliferation by regulating TDG-Mediated DNA demethylation in liver and breast cancer cells","volume":"18","author":"Yan","year":"2020","journal-title":"Mol Ther Oncolytics"},{"issue":"37","key":"10.1016\/j.jnutbio.2025.110227_bib0016","doi-asserted-by":"crossref","first-page":"26793","DOI":"10.1074\/jbc.M703701200","article-title":"Nicotine-induced activation of AMP-activated protein kinase inhibits fatty acid synthase in 3T3L1 adipocytes: a role for oxidant stress","volume":"282","author":"An","year":"2007","journal-title":"J Biol Chem"},{"issue":"6","key":"10.1016\/j.jnutbio.2025.110227_bib0017","doi-asserted-by":"crossref","first-page":"R96","DOI":"10.1186\/bcr2777","article-title":"Fatty acid synthase phosphorylation: a novel therapeutic target in HER2-overexpressing breast cancer cells","volume":"12","author":"Jin","year":"2010","journal-title":"Breast Cancer Res"},{"issue":"16","key":"10.1016\/j.jnutbio.2025.110227_bib0018","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1016\/j.jmb.2016.04.035","article-title":"The nutrient-dependent O-GlcNAc modification controls the expression of liver fatty acid synthase","volume":"428","author":"Baldini","year":"2016","journal-title":"J Mol Biol"},{"issue":"18","key":"10.1016\/j.jnutbio.2025.110227_bib0019","doi-asserted-by":"crossref","first-page":"9814","DOI":"10.3390\/ijms22189814","article-title":"SREBP1-induced glutamine synthetase triggers a feedforward loop to upregulate SREBP1 through Sp1 O-GlcNAcylation and augments lipid droplet formation in cancer cells","volume":"22","author":"Jhu","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0020","article-title":"Limonin alleviates non-alcoholic fatty liver disease by reducing lipid accumulation, suppressing inflammation and oxidative stress","volume":"12","author":"Li","year":"2021","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0021","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.intimp.2018.03.036","article-title":"Micheliolide alleviates hepatic steatosis in db\/db mice by inhibiting inflammation and promoting autophagy via PPAR-gamma-mediated NF-small ka, CyrillicB and AMPK\/mTOR signaling","volume":"59","author":"Zhong","year":"2018","journal-title":"Int Immunopharmacol"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0022","doi-asserted-by":"crossref","DOI":"10.1016\/j.rechem.2025.102389","article-title":"Identification of a 2-phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytes","volume":"16","author":"Hsieh","year":"2025","journal-title":"Results Chem"},{"issue":"1","key":"10.1016\/j.jnutbio.2025.110227_bib0023","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12986-021-00634-4","article-title":"The role and possible mechanism of the long noncoding RNA LINC01260 in nonalcoholic fatty liver disease","volume":"19","author":"Ge","year":"2022","journal-title":"Nutr Metab (Lond)"},{"issue":"1","key":"10.1016\/j.jnutbio.2025.110227_bib0024","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s42003-024-06306-2","article-title":"A DNA demethylase reduces seed size by decreasing the DNA methylation of AT-rich transposable elements in soybean","volume":"7","author":"Wang","year":"2024","journal-title":"Commun Biol"},{"issue":"1","key":"10.1016\/j.jnutbio.2025.110227_bib0025","doi-asserted-by":"crossref","DOI":"10.1177\/1479164121990641","article-title":"Hyperglycemia compromises the ischemia-provoked dedifferentiation of cerebral pericytes through p21-SOX2 signaling in high-fat diet-induced murine model","volume":"18","author":"Wang","year":"2021","journal-title":"Diab Vasc Dis Res"},{"issue":"1","key":"10.1016\/j.jnutbio.2025.110227_bib0026","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/hep.29721","article-title":"Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis","volume":"68","author":"Younossi","year":"2018","journal-title":"Hepatology"},{"issue":"6","key":"10.1016\/j.jnutbio.2025.110227_bib0027","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.cmet.2015.09.025","article-title":"Oncogenic Myc induces expression of glutamine synthetase through promoter demethylation","volume":"22","author":"Bott","year":"2015","journal-title":"Cell Metab"},{"issue":"6","key":"10.1016\/j.jnutbio.2025.110227_bib0028","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/ni.3439","article-title":"Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy","volume":"17","author":"Swamy","year":"2016","journal-title":"Nat Immunol"},{"issue":"3","key":"10.1016\/j.jnutbio.2025.110227_bib0029","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.bbalip.2016.12.005","article-title":"NAFLD is associated with methylation shifts with relevance for the expression of genes involved in lipoprotein particle composition","volume":"1862","author":"Mwinyi","year":"2017","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"issue":"9","key":"10.1016\/j.jnutbio.2025.110227_bib0030","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.3390\/ani10091470","article-title":"Assessment of DNA methylation and oxidative changes in the heart and brain of rats receiving a high-fat diet supplemented with various forms of chromium","volume":"10","author":"Dworzanski","year":"2020","journal-title":"Animals (Basel)"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0031","article-title":"DNA methylation and demethylation in adipocyte biology: roles of DNMT and TET proteins in metabolic disorders","volume":"16","author":"Wu","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"9","key":"10.1016\/j.jnutbio.2025.110227_bib0032","doi-asserted-by":"crossref","DOI":"10.1002\/pmic.202100175","article-title":"O-GlcNAcylation promotes fatty acid synthase activity under nutritional stress as a pro-survival mechanism in cancer cells","volume":"22","author":"Wong","year":"2022","journal-title":"Proteomics"},{"issue":"12","key":"10.1016\/j.jnutbio.2025.110227_bib0033","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1016\/j.bbadis.2018.09.006","article-title":"Consumption of a high fat diet promotes protein O-GlcNAcylation in mouse retina via NR4A1-dependent GFAT2 expression","volume":"1864","author":"Dai","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"12","key":"10.1016\/j.jnutbio.2025.110227_bib0034","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1111\/liv.15059","article-title":"The role of hepatic lipid composition in obesity-related metabolic disease","volume":"41","author":"Willis","year":"2021","journal-title":"Liver Int"},{"issue":"18","key":"10.1016\/j.jnutbio.2025.110227_bib0035","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","article-title":"Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease","volume":"75","author":"Ipsen","year":"2018","journal-title":"Cell Mol Life Sci"},{"issue":"7","key":"10.1016\/j.jnutbio.2025.110227_bib0036","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1210\/clinem\/dgae028","article-title":"Lipidomic analysis reveals alterations in hepatic FA profile associated with MASLD stage in patients with obesity","volume":"109","author":"N\u00fa\u00f1ez-S\u00e1nchez","year":"2024","journal-title":"J Clin Endocrinol Metabol"},{"issue":"1","key":"10.1016\/j.jnutbio.2025.110227_bib0037","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-19459-z","article-title":"FASN inhibition targets multiple drivers of NASH by reducing steatosis, inflammation and fibrosis in preclinical models","volume":"12","author":"O\u2019Farrell","year":"2022","journal-title":"Sci Rep"},{"issue":"10","key":"10.1016\/j.jnutbio.2025.110227_bib0038","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1136\/gut.2010.222844","article-title":"Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C","volume":"60","author":"Miquilena-Colina","year":"2011","journal-title":"Gut"},{"issue":"2","key":"10.1016\/j.jnutbio.2025.110227_bib0039","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1210\/en.2015-1866","article-title":"Hepatocyte-specific disruption of CD36 attenuates fatty liver and improves insulin sensitivity in HFD-Fed Mice","volume":"157","author":"Wilson","year":"2016","journal-title":"Endocrinology"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0040","article-title":"Reversed role of CD36 deficiency in high-fat diet or methionine\/choline-deficient diet-induced hepatic steatosis and steatohepatitis","volume":"16","author":"Zhu","year":"2025","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.jnutbio.2025.110227_bib0041","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.tox.2017.11.013","article-title":"Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction","volume":"393","author":"van Breda","year":"2018","journal-title":"Toxicology"},{"issue":"5","key":"10.1016\/j.jnutbio.2025.110227_bib0042","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/s44321-025-00224-4","article-title":"Liver TET1 promotes metabolic dysfunction-associated steatotic liver disease","volume":"17","author":"Chen","year":"2025","journal-title":"EMBO Mol Med"}],"container-title":["The Journal of Nutritional Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0955286325003894?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0955286325003894?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T18:39:53Z","timestamp":1773945593000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0955286325003894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":42,"alternative-id":["S0955286325003894"],"URL":"https:\/\/doi.org\/10.1016\/j.jnutbio.2025.110227","relation":{},"ISSN":["0955-2863"],"issn-type":[{"value":"0955-2863","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Promoter demethylation and protein O-GlcNAcylation-mediated enhancement of fatty acid synthase contributes to hepatic steatosis and inflammation in MASLD","name":"articletitle","label":"Article Title"},{"value":"The Journal of Nutritional Biochemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jnutbio.2025.110227","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"110227"}}