{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:43:40Z","timestamp":1785926620498,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Talent Project of Anhui Academy of Agricultural Sciences","award":["XJBS-202433"],"award-info":[{"award-number":["XJBS-202433"]}]},{"name":"Talent Project of Anhui Academy of Agricultural Sciences","award":["2026YL044"],"award-info":[{"award-number":["2026YL044"]}]},{"award":["XJBS-202433"],"award-info":[{"award-number":["XJBS-202433"]}],"id":[{"id":"https:\/\/ror.org\/01pw5qp76","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2026YL044"],"award-info":[{"award-number":["2026YL044"]}],"id":[{"id":"https:\/\/ror.org\/01pw5qp76","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Anhui Agriculture Research System"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Overwintering represents a critical bottleneck for farmed fish, during which low temperature and starvation stress frequently co-occur, yet their synergistic effects on fish health remain poorly understood. Here, we exposed Pelteobagrus vachelli, a cold-sensitive freshwater species, to four conditions for 10 days: control (25 \u00b0C, feeding), starvation alone (25 \u00b0C, starvation), cold alone (11 \u00b0C, feeding), and combined cold\u2013starvation (11 \u00b0C, starvation). Hepatic histopathology, antioxidant and liver function indices, gut microbiota (16S rRNA sequencing), and untargeted metabolomics (LC\u2013MS) were integrated to elucidate gut\u2013liver axis mechanisms underlying synergistic injury. Combined stress synergistically aggravated liver injury, as evidenced by hepatocellular vacuolation and necrosis, elevated aspartate aminotransferase (AST), alanine transaminase (ALT), malondialdehyde (MDA), and suppressed total superoxide dismutase (T\u2013SOD), glutathione (GSH), catalase (CAT), and total antioxidant capacity (T\u2013AOC). Two-way ANOVA confirmed significant interactive effects between cold and starvation stress (p &lt; 0.05). Multi-omics revealed that dual stress uniquely activated multiple cell death pathways (FoxO, autophagy, ferroptosis, apoptosis), with marked oxidative phosphorylation (OXPHOS) activation and glutathione depletion\u2014a signature absent under single stressors. Gut microbiota restructuring showed beneficial commensals (Cetobacterium, Prevotella, Lactobacillus) depleted and opportunistic pathogens (Plesiomonas, Pseudomonas, Flavobacterium) enriched, with Plesiomonas identified as the dominant biomarker (LDA score = 5.32). Integrative networks identified these pathogenic genera as hubs linking metabolic dysregulation to liver damage. Collectively, combined cold\u2013starvation induces synergistic liver injury via gut\u2013liver axis disruption, driving metabolic reprogramming and oxidative damage. These findings provide candidate biomarkers for overwintering stress monitoring and inform management strategies to mitigate cold\u2013starvation-induced hepatic injury in aquaculture.<\/jats:p>","DOI":"10.3390\/antiox15080962","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:26:52Z","timestamp":1785778012000},"page":"962","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Starvation Exacerbates Cold-Induced Synergistic Hepatic Injury in Pelteobagrus vachelli via Gut\u2013Liver Axis Disruption and Ferroptosis-Related Metabolic Reprogramming"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9213-6336","authenticated-orcid":false,"given":"Amei","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Fisheries Science, Anhui Academy of Agricultural Sciences, Nongke South Road, Hefei 230031, China"},{"name":"Anhui Province Key Laboratory of Aquaculture & Stock Enhancement, Hefei 230031, China"},{"name":"Anhui Agricultural Germplasm Resource Center, Anhui Academy of Agricultural Sciences, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libo","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Fisheries Science, Anhui Academy of Agricultural Sciences, Nongke South Road, Hefei 230031, China"},{"name":"Anhui Province Key Laboratory of Aquaculture & Stock Enhancement, Hefei 230031, China"},{"name":"Anhui Agricultural Germplasm Resource Center, Anhui Academy of Agricultural Sciences, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-0083","authenticated-orcid":false,"given":"Huaxing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Fisheries Science, Anhui Academy of Agricultural Sciences, Nongke South Road, Hefei 230031, China"},{"name":"Anhui Province Key Laboratory of Aquaculture & Stock Enhancement, Hefei 230031, China"},{"name":"Anhui Agricultural Germplasm Resource Center, Anhui Academy of Agricultural Sciences, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Fisheries Science, Anhui Academy of Agricultural Sciences, Nongke South Road, Hefei 230031, China"},{"name":"Anhui Province Key Laboratory of Aquaculture & Stock Enhancement, Hefei 230031, China"},{"name":"Anhui Agricultural Germplasm Resource Center, Anhui Academy of Agricultural Sciences, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Duan","sequence":"additional","affiliation":[{"name":"Institute of Fisheries Science, Anhui Academy of Agricultural Sciences, Nongke South Road, Hefei 230031, China"},{"name":"Anhui Province Key Laboratory of Aquaculture & Stock Enhancement, Hefei 230031, China"},{"name":"Anhui Agricultural Germplasm Resource Center, Anhui Academy of Agricultural Sciences, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.20506\/rst.38.2.2992","article-title":"Introduction: Improved aquatic animal health management is vital to aquaculture\u2019s role in global food security","volume":"38","author":"Peeler","year":"2019","journal-title":"Rev. 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