{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:41:20Z","timestamp":1793900480985,"version":"4.8.0"},"reference-count":51,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2024ZD0532000"],"award-info":[{"award-number":["2024ZD0532000"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2024ZD0532004"],"award-info":[{"award-number":["2024ZD0532004"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170855"],"award-info":[{"award-number":["82170855"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470873"],"award-info":[{"award-number":["82470873"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020593","name":"Fundamental Research Funds for the Central Universities of Beijing University of Chemical Technology","doi-asserted-by":"publisher","award":["3332022106"],"award-info":[{"award-number":["3332022106"]}],"id":[{"id":"10.13039\/100020593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020593","name":"Fundamental Research Funds for the Central Universities of Beijing University of Chemical Technology","doi-asserted-by":"publisher","award":["3332021094"],"award-info":[{"award-number":["3332021094"]}],"id":[{"id":"10.13039\/100020593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008235","name":"Peking Union Medical College Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008235","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011176","name":"Peking Union Medical College","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011176","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,12,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Metabolism\u2010associated steatotic liver disease (MASLD) encompasses a broad spectrum of liver disorders characterized by systemic metabolic imbalance, and its prevalence is increasing. Current therapeutic strategies are limited, highlighting the need for novel interventions. Ferroptosis has emerged as a significant factor in MASLD pathogenesis, suggesting a potential target for therapeutic development. A MASLD model was established in mice via a high\u2010fat diet. The mice in the betaine\u2010supplemented group were fed a diet containing 0.3% (w\/w) betaine from the start of the intervention. Metabolic indicators, liver histology, and ferroptosis markers, such as lipid peroxidation and iron homeostasis, were evaluated. In\u00a0vitro, AML12 cells were cultured with palmitic acid to mimic a high\u2010fat environment, and the preventive effects of betaine on ferroptosis markers were assessed. To further validate the antiferroptotic actions of betaine, erastin was used in both in\u00a0vivo and in\u00a0vitro models. In this study, betaine attenuated HFD\u2010induced hepatic steatosis, effectively reducing lipid peroxidation and iron accumulation both in\u00a0vivo and in\u00a0vitro. Furthermore, betaine also counteracted erastin\u2010induced hepatocyte ferroptosis. Mechanistic investigations revealed the activation of the Nrf2\/GPX4 axis by betaine, elucidating its antiferroptotic mechanism. This study provides preliminary evidence that, in an early\u2010stage, preventive murine model, betaine could ameliorate hepatic steatosis by limiting ferroptosis, in association with Nrf2 pathway activation. These findings suggest the ferroptosis\u2013Nrf2 axis as a potential target for preventive strategies and warrant further evaluation in advanced disease models and clinical settings.<\/jats:p>","DOI":"10.1096\/fj.202501416rrrr","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:49:47Z","timestamp":1766155787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Betaine Attenuates High\u2010Fat\u2010Diet\u2010Induced Metabolism\u2010Associated Steatotic Liver Disease via the Inhibition of Ferroptosis Through the Nrf2\/GPX4 Axis"],"prefix":"10.1096","volume":"39","author":[{"given":"Xiao\u2010jun","family":"Zhai","sequence":"first","affiliation":[{"name":"Department of Endocrinology Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital  Beijing China"},{"name":"Department of Anesthesiology Ministry of Health, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010ru","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze\u2010rui","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0890-0113","authenticated-orcid":false,"given":"Dong\u2010mei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics, Metabolism Beijing Children's Hospital, Capital Medical University, National Center for Children's Health  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7322-393X","authenticated-orcid":false,"given":"Jie\u2010ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital  Beijing China"},{"name":"Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2022.0367"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.02.003"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/20420188221145549"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122327"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-024-02045-0"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2298-2"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-023-01969-y"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28124824"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116263"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani12121530"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods11060881"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.751436"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.809642"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2015.08.007"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-016-1232-y"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-10-60"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10051081"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2023.0272"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14446"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1712108"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crfs.2023.100663"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109297"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu8100646"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32511-3"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147571"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.21855"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.11.043"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927620024265"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2013.11.007"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.01.039"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2001.04129.x"},{"issue":"8","key":"e_1_2_13_33_1","first-page":"722","article-title":"Efficacy and Safety of Oral Betaine Glucuronate in Non\u2010Alcoholic Steatohepatitis. A Double\u2010Blind, Randomized, Parallel\u2010Group, Placebo\u2010Controlled Prospective Clinical Study","volume":"50","author":"Miglio F.","year":"2000","journal-title":"Arzneimittel\u2010Forschung"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v26.i38.5745"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23239"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2020.03.011"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102570"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.10.005"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.12.088"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12111926"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202200341"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2023.0028"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2017"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.06.014"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.150"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11122377"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-020-02362-6"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2014.04.010"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115415"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2023.05.003"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.54113"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01769-5"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202501416RRRR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202501416RRRR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202501416RRRR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:54:36Z","timestamp":1770288876000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202501416RRRR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":51,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2025,12,31]]}},"alternative-id":["10.1096\/fj.202501416RRRR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202501416rrrr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]},"assertion":[{"value":"2025-04-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71315"}}