{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T01:36:02Z","timestamp":1780796162084,"version":"3.54.1"},"reference-count":69,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2023-00248268"],"award-info":[{"award-number":["RS-2023-00248268"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Toxicant-associated steatohepatitis (TASH) is caused by environmental toxicants rather than metabolic factors; however, its pathogenic mechanisms remain poorly understood. Polychlorinated biphenyl 138 (PCB138), a persistent lipophilic contaminant that bioaccumulates in adipose tissue, may promote TASH through unclear mechanisms. In this study, we investigated whether PCB138 induces liver injury via hepatic iron dysregulation and adipose-liver inflammatory signaling. Male C57BL\/6 mice received intraperitoneal PCB138 (1, 5, 10, or 50 mg\/kg, four injections over six weeks). HepG2 hepatocytes were treated with PCB138 with or without ferric ammonium citrate (FAC), and PCB138-exposed 3T3-L1 adipocytes were co-cultured with HepG2 cells using a Transwell system. PCB138 dose-dependently increased serum transaminase and hepatic non-heme iron levels, with Hamp upregulation, macrophage infiltration, and fibrosis. In HepG2 cells, PCB138 synergized with FAC to elevate intracellular Fe2+, induced Hamp, suppressed Slc40a1, and upregulated inflammatory\/profibrotic genes. In Transwell co-cultures, TNF-\u03b1, IL-6, and IL-1\u03b2 from PCB138-exposed adipocytes amplified hepatic iron dysregulation and fibrotic responses. These findings demonstrated that PCB138 induced TASH through hepatic iron dysregulation and adipose-derived inflammatory signaling, independent of steatosis. These results highlighted the iron\u2013adipose axis as a novel mechanistic link between PCB138 exposure and liver injury, offering potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/toxics13110932","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:28:43Z","timestamp":1761888523000},"page":"932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Polychlorinated Biphenyl 138 Induces Toxicant-Associated Steatohepatitis via Hepatic Iron Overload and Adipose Inflammation"],"prefix":"10.3390","volume":"13","author":[{"given":"Hyeon","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Anatomy, Inje University College of Medicine, Busan 47392, Republic of Korea"},{"name":"Department of Molecular Biology, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5408-2863","authenticated-orcid":false,"given":"Mi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4279-7563","authenticated-orcid":false,"given":"Seung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-7454","authenticated-orcid":false,"given":"Byung-Jun","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joong-Gook","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Center, Dongnam Intitute of Radiological Sciences (DIRAMS), Busan 46033, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4377-5792","authenticated-orcid":false,"given":"Dae","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-6737","authenticated-orcid":false,"given":"Young","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Busan 49201, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JaeHun","family":"Cheong","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8487-3655","authenticated-orcid":false,"given":"Hye","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Accacha, S., Barillas-Cerritos, J., Srivastava, A., Ross, F., Drewes, W., Gulkarov, S., De Leon, J., and Reiss, A.B. 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