{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:53:55Z","timestamp":1791356035539,"version":"4.3.1"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["SR\/S2\/JCB\u201080)\/2012"],"award-info":[{"award-number":["SR\/S2\/JCB\u201080)\/2012"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>MASLD is a chronic liver disease characterized by excess fat build up in the liver. Elevated expression of FTO has been implicated in steatosis and MASLD development. There is no standard treatment for MASLD. Here we investigated the hepatoprotective effects of entacapone\u2014a pharmacological inhibitor of FTO\u2014in preclinical models. Entacapone was administered intra\u2010peritoneally at a daily dose of 10 or 30\u2009mg in a MASLD mouse model. Changes in obesity, lipid accumulation and liver fibrosis were monitored during the treatment period. Biomarkers of hepatic and metabolic functions were measured by bioanalyzer. The FTO and metabolic gene transcripts were quantitated by RT\u2010qPCR whereas the m6A levels were measured by ELISA. The hepatic expression of FTO protein in mice and clinical samples (MASLD, MASH and cirrhosis) was visualized by immunohistochemical staining. The regulation of FTO gene by entacapone was also investigated in cell culture. Treatment of mice with entacapone led to a significant reduction in obesity and hepatic fat build\u2010up as well as normalization of metabolic functions and MAS score. The m6A levels in gene transcripts were high and coincided with reduced expression of FTO, lipogenic and inflammatory genes. Interestingly, FTO isoforms FTO\u20101 FTO\u20105 and FTO\u201012 were overexpressed in the MASLD patients whereas no change in FTO\u20105 and FTO\u201012 levels was observed in MASH and cirrhosis patients. Further, FTO expression was down\u2010regulated by entacapone in immortalized hepatocytes. This study highlights the therapeutic potential of entacapone in the management of metabolic liver disease by targeting the FTO demethylase activity.<\/jats:p>","DOI":"10.1002\/ddr.70326","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T15:18:59Z","timestamp":1781018339000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Entacapone Ameliorates MASLD by Inhibiting FTO Demethylase Activity"],"prefix":"10.1002","volume":"87","author":[{"given":"Sunita","family":"Giri","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepti","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Chemistry J.C. Bose University of Science and Technology  Faridabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2024.103043"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cld.740"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/15376516.2023.2244061"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2018.02.003"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja3064149"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1033-z"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100714"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.880298"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.03.039"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1141634"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1151710"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.36922\/ITPS025140019"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.25259\/IJMR_945_2025"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.6339"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.624112"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-2601"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2022.04.014"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.03.006"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1276"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109766"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.687"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2022.100628"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0259"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-387817-5.00025-X"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103661"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2022.02.010"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.09.086"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11060786"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-024-00629-2"},{"key":"e_1_2_10_32_1","unstructured":"Manregazza S. 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