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The liver is central to metabolic homeostasis and immune defense, and its physiological stability is critical for fish health. The present study evaluated the hepatic physiological responses of\n                    <jats:italic>Trachinotus ovatus<\/jats:italic>\n                    following a 7-day exposure to high-temperature (HT) stress, including alterations in histology, oxidative stress, iron homeostasis, inflammation, immunity, apoptosis, and bile acid (BA) metabolism. HT stress induced alterations in liver histology and disrupted redox homeostasis, accompanied by enhanced Nrf2-mediated antioxidant signaling and changes in antioxidant defense enzyme activities and peroxide levels. Iron homeostasis and lipid peroxide defense exhibited complex alterations, including Fe levels and\n                    <jats:italic>NCOA4<\/jats:italic>\n                    expression were increased, accompanied by compensatory upregulation of iron-homeostasis genes (\n                    <jats:italic>FTH1<\/jats:italic>\n                    ,\n                    <jats:italic>FPN1<\/jats:italic>\n                    , and\n                    <jats:italic>NFS1<\/jats:italic>\n                    ) and antioxidant defense genes (\n                    <jats:italic>GPx4<\/jats:italic>\n                    ,\n                    <jats:italic>SLC7A11<\/jats:italic>\n                    , and\n                    <jats:italic>p53<\/jats:italic>\n                    ). However, reduced lipid peroxidation products (LPO and MDA) suggested that these changes reflected regulatory adaptation rather than the execution of ferroptosis. HT stress induced hepatic inflammatory and immune responses, characterized by activation of pro-inflammatory signaling, dysregulated anti-inflammatory regulation, downregulation of\n                    <jats:italic>IL-8<\/jats:italic>\n                    expression, and downregulation of the immunoglobulin genes\n                    <jats:italic>IgM<\/jats:italic>\n                    and\n                    <jats:italic>IgT<\/jats:italic>\n                    . Apoptosis-related genes showed divergent expression patterns, with\n                    <jats:italic>CHOP<\/jats:italic>\n                    ,\n                    <jats:italic>Casp-9<\/jats:italic>\n                    , and\n                    <jats:italic>Casp-3<\/jats:italic>\n                    being upregulated, whereas\n                    <jats:italic>CytC<\/jats:italic>\n                    was downregulated. Furthermore, BA metabolism was affected, as shown by reductions in total BA pool size and free BA levels, along with the upregulated expression of BA metabolism-related genes (\n                    <jats:italic>FXR<\/jats:italic>\n                    ,\n                    <jats:italic>SULT1<\/jats:italic>\n                    , and\n                    <jats:italic>UGT8<\/jats:italic>\n                    ). Three metabolites, cholic acid, chenodeoxycholic acid, and 7-ketolithocholic acid were identified as potential biomarkers. Collectively, these findings suggest that HT stress impaired hepatic physiological homeostasis in\n                    <jats:italic>T. ovatus<\/jats:italic>\n                    , accompanied by tissue architecture disruption, redox imbalance, inflammatory responses, immune suppression, BA metabolic remodeling, and coordinated changes in iron homeostasis and apoptosis-related regulatory pathways.\n                  <\/jats:p>","DOI":"10.1007\/s44154-026-00344-y","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T09:21:44Z","timestamp":1792401704000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-temperature stress response in the liver of Trachinotus ovatus: a cascade of oxidative stress, immunity, and bile acid metabolic reprogramming"],"prefix":"10.1007","volume":"6","author":[{"given":"Ruijie","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianchang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukai","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"344_CR1","doi-asserted-by":"publisher","first-page":"114152","DOI":"10.1007\/s11356-023-30386-y","volume":"30","author":"MS Alfons","year":"2023","unstructured":"Alfons MS, Ibrahim AThA, Harabawy ASA, Al-salahy MB, Badr G (2023) Cytoprotective effect of propolis on heat stress induces alteration to histological, ultrastructural, and oxidative stress in catfish (Clarias gariepinus). 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