{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:00:06Z","timestamp":1780340406953,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21377062"],"award-info":[{"award-number":["21377062"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012154","name":"Graduate Research and Innovation Projects of Jiangsu Province","doi-asserted-by":"publisher","award":["KYCX19_2083"],"award-info":[{"award-number":["KYCX19_2083"]}],"id":[{"id":"10.13039\/501100012154","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The persistent environmental pollutant 2,3,7,8\u2010tetrachlorodibenzo\u2010p\u2010dioxin (TCDD) has been implicated in hepatic lipid metabolism disorders and steatosis. However, the precise mechanisms underlying TCDD\u2010induced hepatic lipid deposition remain incompletely elucidated. Mitofusin 2 (MFN2), a key mitochondrial dynamics protein, plays a critical role in lipid metabolism, as its deficiency leads to metabolic dysregulation. In this study, we investigate the role of\n                    <jats:italic>MFN2<\/jats:italic>\n                    in TCDD\u2010induced lipid deposition. Our findings demonstrate that TCDD exposure significantly reduces MFN2 protein expression both in\u00a0vivo and in\u00a0vitro, while concomitantly decreasing mitochondrial membrane potential and increasing reactive oxygen species (ROS) levels in Huh7 cells. Notably, overexpression of\n                    <jats:italic>MFN2<\/jats:italic>\n                    effectively mitigates TCDD\u2010induced pathological effects, preventing lipid accumulation, restoring mitochondrial membrane potential, and reducing ROS levels. Mechanistically, although TCDD does not alter the\n                    <jats:italic>MFN2<\/jats:italic>\n                    mRNA expression, it promotes protein degradation through enhanced ubiquitination in\u00a0vitro. These findings demonstrate that TCDD induces lipid accumulation in Huh7 cells through ubiquitination\u2010mediated degradation of MFN2. Our study thus identifies\n                    <jats:italic>MFN2<\/jats:italic>\n                    as a novel target in TCDD\u2010induced hepatic steatosis.\n                  <\/jats:p>","DOI":"10.1002\/jat.4890","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T23:29:36Z","timestamp":1754954976000},"page":"250-258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TCDD Induces Hepatocytes Lipid Deposition via Downregulation of MFN2"],"prefix":"10.1002","volume":"46","author":[{"given":"Changming","family":"Xing","sequence":"first","affiliation":[{"name":"School of Public Health Nantong University  Nantong Jiangsu China"},{"name":"Zhangjiagang City Center for Disease Control and Prevention  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Ai","sequence":"additional","affiliation":[{"name":"School of Public Health Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Public Health Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiping","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Public Health Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxi","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Public Health Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangfei","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Public Health 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