{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:05:32Z","timestamp":1789967132174,"version":"4.0.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant that disturbs hepatic lipid metabolism. The androgen receptor (AR) protects hepatic lipid homeostasis, but whether BaP interferes with AR nuclear translocation through aryl hydrocarbon receptor (AhR) activation to cause metabolic disorders remains unknown\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      . This study aimed to clarify BaP-mediated regulation of AR signaling and its dependence on the AhR pathway during hepatic lipid metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An androgen-deficient mouse model was established by bilateral orchiectomy, and lipid disorders were induced by BaP (0.9\u00a0mg\u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00a0day\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). HepG2 cells were treated with BaP (1\u00a0\u03bcmol\u00a0L\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) with or without dihydrotestosterone (DHT, 1\u00a0\u03bcmol\u00a0L\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) or AhR antagonist CH223191 (1\u00a0\u03bcmol\u00a0L\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). Hepatic injury was evaluated by HE and Oil Red O staining. Serum lipids, liver function, AR nuclear translocation, and expression of lipid-related genes were measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In androgen-present mice, BaP induced liver injury and lipid accumulation, inhibited AR nuclear translocation, reduced \u03b2-oxidation genes (PGC-1\u03b1, CPT1A, PPAR\u03b1), and increased lipogenic genes (SREBP2, HMGCR, LXR\u03b1). In androgen-deficient mice, BaP promoted AR translocation and improved lipid metabolism. In HepG2 cells, BaP alone enhanced AR translocation and fatty acid oxidation, while BaP + DHT inhibited AR translocation and promoted lipogenesis. All effects were reversed by CH223191.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BaP exerts bidirectional regulation on AR via AhR: it exerts an anti-androgenic in androgen-replete conditions and regulates AR-related signaling pathways in androgen deficiency. The AhR\u2013AR axis is a key target for preventing BaP-induced hepatic steatosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1880959","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:29:29Z","timestamp":1789964969000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of BaP- regulated hepatic lipid metabolism via AhR activation and AR modulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Han","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Inner Mongolia Autonomous Region Engineering Research Center for New Drug Screening, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Su","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulu","family":"Du","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Inner Mongolia Autonomous Region Engineering Research Center for New Drug Screening, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Inner Mongolia Autonomous Region Engineering Research Center for New Drug Screening, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Inner Mongolia Autonomous Region Engineering Research Center for New Drug Screening, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Inner Mongolia Autonomous Region Engineering Research Center for New Drug Screening, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoquan","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuya","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Inner Mongolia Autonomous Region Engineering Research Center for New Drug Screening, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhong","family":"Huangfu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhou","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Pharmacy Teaching-Research Section, School of Medicine, Qingdao Binhai University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1007\/s12072-024-10692-4","article-title":"Epidemiology, pathophysiology and clinical aspects of hepatocellular carcinoma in MAFLD patients","volume":"18","author":"Argenziano","year":"2024","journal-title":"Hepatol. 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