{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T04:38:25Z","timestamp":1794285505081,"version":"4.9.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC2000500 2021YFA1301104 2021YFC2301804"],"award-info":[{"award-number":["2018YFC2000500 2021YFA1301104 2021YFC2301804"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81790613 81570512"],"award-info":[{"award-number":["81790613 81570512"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common chronic liver diseases with limited treatment options.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Ob\/ob mice (6 weeks old) were fed with the Control diet or amylin liver NASH (AMLN) diet for 24 weeks to establish the NASH, the AMLN diet-fed mice were treated with obeticholic acid (OCA), ferrostatin-1 (Fer-1) or their combination for 7 weeks. Finally, various clinical profiles were assessed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Our results indicate that Fer-1 exerts better effects on improving body weight, blood glucose levels, transaminase levels and insulin resistance than OCA. OCA has a profound effect on ameliorating lipid accumulation. OCA and Fer-1 differentially inhibit the activation of hepatic Kupffer cells and HSCs. The combination of OCA and Fer-1 significantly reduces inflammation and protects mice against liver oxidative stress. OCA and Fer-1 differentially reshape the intestinal microbiota and affect the hepatic lipidome.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Our study compares the effects of OCA, Fer-1 and their combination on various clinical profiles in NASH. These data demonstrate that different drug combinations results in different improvements, and these discoveries provide a reference for the use of the OCA, Fer-1 and their combination in the clinical treatment of NAFLD\/NASH.<\/jats:p>","DOI":"10.3389\/fphar.2022.1081553","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T04:43:00Z","timestamp":1671165780000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Obeticholic acid and ferrostatin-1 differentially ameliorate non-alcoholic steatohepatitis in AMLN diet-fed ob\/ob mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Shengjie","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoxiang","family":"Zhuge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaicen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafeng","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyi","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.jhep.2019.06.011","article-title":"Obeticholic acid may increase the risk of gallstone formation in susceptible patients","volume":"71","author":"Al-Dury","year":"2019","journal-title":"J. hepatology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1042\/CS20030326","article-title":"Increase in long-chain polyunsaturated fatty acid n - 6\/n - 3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease","volume":"106","author":"Araya","year":"1979","journal-title":"Clin. 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