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Although the recent studies have demonstrated that PCB exposure leads to nonalcoholic fatty liver disease (NAFLD), the underlying mechanism has remained unsolved. In this study, we examined the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, and PCB 126 in C57BL\/6 mice. Male C57Bl\/6 mice were fed a standard diet or a 60% high\u2010fat diet and exposed to Aroclor 1260 (10\u00a0mg\/kg or 20\u2009mg\/kg) or PCB 126 (1\u00a0mg\/kg or 5\u00a0mg\/kg) by intraperitoneal injection for a total of four injections (2, 3, 4, and 5\u2009weeks) for 6\u2009weeks. In mice, both Aroclor 1260 and PCB 126\u2010induced liver damage, hepatic steatosis and inflammation. We also observed that PCB exposure\u2010induced hepatic iron overload (HIO). We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable therapeutic target for NAFLD patients. Thus, we further examined whether hepatic STAMP2 is involved in PCB\u2010induced NAFLD. We observed that hepatic STAMP2 was significantly decreased in PCB\u2010induced NAFLD models in vivo and in vitro. Furthermore, overexpression of hepatic STAMP2 using an adenoviral delivery system resulted in improvement of PCB\u2010induced steatosis and HIO in vivo and in vitro. Our findings indicate that enhancing hepatic STAMP2 expression represents a potential therapeutic avenue for the treatment of PCB exposure\u2010induced NAFLD.<\/jats:p>","DOI":"10.1002\/tox.23589","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T10:06:55Z","timestamp":1653559615000},"page":"2223-2234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hepatic <scp>STAMP2<\/scp> alleviates polychlorinated biphenyl\u2010induced steatosis and hepatic iron overload in <scp>NAFLD<\/scp> models"],"prefix":"10.1002","volume":"37","author":[{"given":"Hye Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology and BK21 program, Department of Translational Biomedical Science Dong\u2010A University College of Medicine  Busan Republic of Korea"},{"name":"Department of Oral Microbiology and Oral Genomics Research Center, School of Dentistry Pusan National University  Busan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology and BK21 program, Department of Translational Biomedical Science Dong\u2010A University College of Medicine  Busan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joon Beom","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology and BK21 program, Department of Translational Biomedical Science Dong\u2010A University College of Medicine  Busan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kangeun","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology and BK21 program, Department of Translational Biomedical Science Dong\u2010A University College of Medicine  Busan Republic of 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