{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:42:52Z","timestamp":1791398572569,"version":"4.3.3"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"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 (NRF)","doi-asserted-by":"publisher","award":["2022R1F1A1064538"],"award-info":[{"award-number":["2022R1F1A1064538"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by lipid accumulation within the liver. The pathogenesis underlying its development is poorly understood. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and a group 1 carcinogen. The aryl hydrocarbon receptor activation by B[a]P induces cytochrome P450 (CYP) enzymes, contributing to hepatic lipid accumulation. However, the molecular mechanism through which the B[a]P-mediated induction of CYP enzymes causes hepatic lipid accumulation is unknown. This research was conducted to elucidate the role of CYP1B1 in regulating B[a]P-induced lipid accumulation within hepatocytes. B[a]P increased hepatic lipid accumulation, which was mitigated by CYP1B1 knockdown. An increase in the mammalian target of rapamycin (mTOR) by B[a]P was specifically reduced by CYP1B1 knockdown. The reduction of mTOR increased the expression of autophagic flux-related genes and promoted phagolysosome formation. Both the expression and translocation of TFE3, a central regulator of lipophagy, were induced, along with the expression of lipophagy-related genes. Conversely, enhanced mTOR activity reduced TFE3 expression and translocation, which reduced the expression of lipophagy-related genes, diminished phagolysosome production, and increased lipid accumulation. Our results indicate that B[a]P-induced hepatic lipid accumulation is caused by CYP1B1-induced mTOR and the reduction of lipophagy, thereby introducing novel targets and mechanisms to provide insights for understanding B[a]P-induced MASLD.<\/jats:p>","DOI":"10.3390\/ijms25021324","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T03:50:22Z","timestamp":1705895422000},"page":"1324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Regulation of Benzo[a]pyrene-Induced Hepatic Lipid Accumulation through CYP1B1-Induced mTOR-Mediated Lipophagy"],"prefix":"10.3390","volume":"25","author":[{"given":"Kyung-Bin","family":"Bu","sequence":"first","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Kyoung","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3145-8458","authenticated-orcid":false,"given":"Jung-Suk","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrgastro.2010.21","article-title":"Pathology of Nonalcoholic Fatty Liver Disease","volume":"7","author":"Brunt","year":"2010","journal-title":"Nat. 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