{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:59:17Z","timestamp":1785301157197,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>BackgroundHigh\u2010sugar, high\u2010fat diets (HSDFD) can lead to hepatic dysfunction, but the molecular mechanisms underlying protective compounds like sesamin remain unclear MethodsWe employed a multi\u2010faceted approach combining in silico and in\u00a0vivo techniques. Utilizing the AlphaFold database, we screened multi\u2010species proteomes to identify potential sesamin targets. Molecular dynamics simulations and MM\u2010PBSA analysis were used to characterize sesamin\u2010protein interactions. In\u00a0vivo studies included single\u2010cell RNA sequencing of hepatocytes from HSDFD\u2010fed mice. We validated our findings using cellular thermal shift assays (CETSA), drug affinity responsive target stability (DARTS) assays, Western blotting, and qPCR. ResultsHSDFD induced significant redistribution of hepatocyte subpopulations with high CYP1A2 abundance. Computational analysis identified CYP1A2 as a direct target of sesamin, with species\u2010specific interaction patterns. Sesamin exhibited stable binding to CYP1A2, modulating its activity through subtle conformational changes. Key residues F451 and I386 were crucial for sesamin's regulation of CYP1A2\u2010mediated ROS production. Sesamin supplementation ameliorated HSDFD\u2010induced hepatic dysfunction by modulating fatty acid metabolism and oxidative stress responses. ConclusionOur study unveils CYP1A2 as a key molecular target of sesamin in HSDFD\u2010induced hepatic dysfunction, providing new insights into potential therapeutic strategies for metabolic liver disorders.<\/jats:p>","DOI":"10.1111\/jcmm.71274","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:43:09Z","timestamp":1784292189000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sesamin Ameliorates High\u2010Sugar, High\u2010Fat Diet\u2010Induced Hepatic Dysfunction via\n                    <scp>CYP1A2<\/scp>\n                    \u2010Mediated Regulation of Lipid Metabolism and Oxidative Stress"],"prefix":"10.1111","volume":"30","author":[{"given":"Xiliang","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Heart Center of Henan Provincial People's Hospital, Fuwai Central China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Luzhou People's Hospital  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Shaw Hospital, School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Heart Center of Henan Provincial People's Hospital, Fuwai Central China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2214-9519","authenticated-orcid":false,"given":"Yi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Affiliated Hospital, Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13070787"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28217255"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c02794"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11010188"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuae089"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7379"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14194079"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26040883"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116240"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107356"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115768"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173417"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232415482"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.3407"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2021.1881438"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753944715586178"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/c4fo00322e"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2016.06.015"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2005.09.013"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007487\u2010w"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003819\u20102"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1061"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2023113898"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2023.06.020"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200221999210101233135"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2021.2007553"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0300\u2010483x(02)00088\u20104"},{"key":"e_1_2_10_29_1","first-page":"173","article-title":"Human Cytochrome P4501a2, IARC Sci Publ","volume":"148","author":"Landi M. 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