{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:41:44Z","timestamp":1785415304960,"version":"3.56.0"},"reference-count":94,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Program of Guangdong Province","award":["2019B030316022"],"award-info":[{"award-number":["2019B030316022"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M772603"],"award-info":[{"award-number":["2025M772603"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2025M772603"],"award-info":[{"award-number":["2025M772603"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Research on breeding technology of candidate species for Guangdong modern marine ranching","award":["2025-MRB-00-001"],"award-info":[{"award-number":["2025-MRB-00-001"]}]},{"name":"Research on breeding technology of candidate species for Guangdong modern marine ranching","award":["2024-MRB-00-001"],"award-info":[{"award-number":["2024-MRB-00-001"]}]},{"name":"Guangdong Financial Budget","award":["(2023) No. 6"],"award-info":[{"award-number":["(2023) No. 6"]}]},{"name":"China-ASEAN Fisheries Resources Conservation and Exploitation","award":["CAMC-2018F"],"award-info":[{"award-number":["CAMC-2018F"]}]},{"DOI":"10.13039\/501100001809","name":"The Natural Science Foundation of China","doi-asserted-by":"crossref","award":["42177262"],"award-info":[{"award-number":["42177262"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"2023 National Undergraduate Innovation and Entrepreneurship Training Program","award":["202311078043"],"award-info":[{"award-number":["202311078043"]}]},{"name":"platform funding support from Guangzhou University"},{"id":[{"id":"https:\/\/ror.org\/05ar8rn06","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Epinephelus akaara is one of the aquaculture species with high commercial value in the aquaculture industry in the Asia-Pacific region. However, acute hypoxia is widespread in the intensive farming and live fish transportation of E. akaara, which seriously hinders the rapid development of the E. akaara farming industry. In this study, transcriptome sequencing (RNA-seq) was conducted on the liver tissues of E. akaara after hypoxia (0.6 \u00b1 0.1 mg\/L) for 1, 3, 6 and 9 h. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that key signaling pathways such as IL-17, HIF-1, TNF and PI3K\/Akt were significantly enriched in the hypoxia treatment groups (Hy6 and Hy9). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses revealed that genes linked to energy metabolism, immune response and apoptosis changed significantly in the liver and brain at 6 h and 9 h under acute hypoxia. In addition, three metabolism-related enzymes (GLU, LDH and PK) and two immune-related enzymes (ALT and AKP) all changed significantly at 6 h and 9 h, indicating that 6\u20139 h was the critical period for physiological stress of E. akaara. In conclusion, these results indicate that E. akaara mediated the organism\u2019s tolerance and adaptation to hypoxic stress by regulating energy metabolism, immune response and apoptosis. This study enriches the regulatory mechanism by which E. akaara adapts to acute hypoxia and is conducive to the breeding of hypoxia-tolerant E. akaara strains.<\/jats:p>","DOI":"10.3390\/ani16101469","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T10:50:52Z","timestamp":1778496652000},"page":"1469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liver Transcriptome Analysis Revealed the Physiological Response Mechanism of Red-Spotted Grouper (Epinephelus akaara) Under Acute Hypoxic Stress"],"prefix":"10.3390","volume":"16","author":[{"given":"Yukun","family":"Huang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqin","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiya","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyin","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5324-8303","authenticated-orcid":false,"given":"Jinhui","family":"Wu","sequence":"additional","affiliation":[{"name":"Agro-Tech Extension Center of Guangdong Province, Guangzhou 510520, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianguang","family":"Cai","sequence":"additional","affiliation":[{"name":"Shenzhen Haijuyuan Aquacture Technology Co., Ltd., Shenzhen 518120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Cui","sequence":"additional","affiliation":[{"name":"Shenzhen Haijuyuan Aquacture Technology Co., Ltd., Shenzhen 518120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Along","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Shu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ecoinf.2009.09.015","article-title":"The River Mesta Case Study: A Qualitative Model of Dissolved Oxygen in Aquatic Ecosystems","volume":"4","author":"Nakova","year":"2009","journal-title":"Ecol. Inform."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1017\/wat.2024.6","article-title":"Water Quality Management in Aquaculture","volume":"2","author":"Yusoff","year":"2024","journal-title":"Camb. Prism. Water"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1007\/s10695-019-00614-9","article-title":"Fish Response to Hypoxia Stress: Growth, Physiological, and Immunological Biomarkers","volume":"45","author":"Monier","year":"2019","journal-title":"Fish Physiol. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"111060","DOI":"10.1016\/j.cbpa.2021.111060","article-title":"Effects of Hypoxia and Hyperoxia on Growth Parameters and Transcription Levels of Growth, Immune System and Stress Related Genes in Rainbow Trout","volume":"262","author":"Aksakal","year":"2021","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"740120","DOI":"10.1016\/j.aquaculture.2023.740120","article-title":"Integrated mRNA-Seq and miRNA-Seq Analysis Reveals the microRNAs-Transcription Factor-mRNA Regulatory Network of Pearl Gentian Grouper under Acute Hypoxia","volume":"578","author":"Liang","year":"2024","journal-title":"Aquaculture"},{"key":"ref_6","first-page":"1","article-title":"Chapter 1 The Hypoxic Environment","volume":"Volume 27","author":"Richards","year":"2009","journal-title":"Fish Physiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10872-011-0006-7","article-title":"Long-Term Changes of Dissolved Oxygen, Hypoxia, and the Responses of the Ecosystems in the East China Sea from 1975 to 1995","volume":"67","author":"Ning","year":"2011","journal-title":"J. Oceanogr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"740827","DOI":"10.1016\/j.aquaculture.2024.740827","article-title":"Acute Hypoxia and Reoxygenation Alters Glucose and Lipid Metabolic Patterns in Hulong Hybrid Grouper (Epinephelus fuscoguttatus\u2640 \u00d7 E. lanceolatus\u2642)","volume":"586","author":"Wang","year":"2024","journal-title":"Aquaculture"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s11160-023-09793-4","article-title":"An Overview of the Mechanisms Underlying Hypoxia Tolerance Differences in Aquatic Animals and Their Inspirations for Aquaculture","volume":"33","author":"Shen","year":"2023","journal-title":"Rev. Fish Biol. Fish."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0044-8486(00)00316-1","article-title":"Effects of Hypoxia on Growth and Metabolism of Juvenile Turbot","volume":"188","author":"Pichavant","year":"2000","journal-title":"Aquaculture"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.aquaculture.2011.11.036","article-title":"Effects of Cyclic Environmental Hypoxia on Physiology and Feed Intake of Post-Smolt Atlantic Salmon: Initial Responses and Acclimation","volume":"326\u2013329","author":"Remen","year":"2012","journal-title":"Aquaculture"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"735449","DOI":"10.1016\/j.aquaculture.2020.735449","article-title":"The Effects of Constant and Cyclical Hypoxia on the Survival, Growth and Metabolic Physiology of Incubating Atlantic Salmon (Salmo salar)","volume":"527","author":"Wood","year":"2020","journal-title":"Aquaculture"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.aquaculture.2017.06.020","article-title":"Gill Remodeling in Response to Hypoxia and Temperature Occurs in the Hypoxia Sensitive Blunt Snout Bream (Megalobrama amblycephala)","volume":"479","author":"Wu","year":"2017","journal-title":"Aquaculture"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1039\/C4LC00717D","article-title":"A Microfluidic System for Studying the Behavior of Zebrafish Larvae under Acute Hypoxia","volume":"15","author":"Erickstad","year":"2015","journal-title":"Lab A Chip"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1111\/are.12146","article-title":"Temperature and Dissolved Oxygen Influence Growth and Digestive Enzyme Activities of Yellowtail Kingfish Seriola lalandi (Valenciennes, 1833)","volume":"45","author":"Bowyer","year":"2014","journal-title":"Aquac. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"738747","DOI":"10.1016\/j.aquaculture.2022.738747","article-title":"Hypoxia Alters Glucose and Lipid Metabolisms in Golden Pompano (Trachinotus blochii)","volume":"562","author":"Jiang","year":"2023","journal-title":"Aquaculture"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1139\/cjz-2013-0247","article-title":"Mitochondria: A Multimodal Hub of Hypoxia Tolerance","volume":"92","author":"Pamenter","year":"2014","journal-title":"Can. J. Zool."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1053\/j.gastro.2015.11.043","article-title":"Circadian Clock Control of Liver Metabolic Functions","volume":"150","author":"Reinke","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/hep.25497","article-title":"Hypoxia and Hypoxia Inducible Factors: Diverse Roles in Liver Diseases","volume":"55","author":"Nath","year":"2012","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/4687685","article-title":"Histological, Genotoxic, and Biochemical Effects on Cnesterodon decemmaculatus (Jenyns 1842) (Cyprinodontiformes, Poeciliidae): Early Response Bioassays to Assess the Impact of Receiving Waters","volume":"2019","author":"Ossana","year":"2019","journal-title":"J. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ecoenv.2005.10.012","article-title":"Histological Changes in the Liver of Oreochromis mossambicus (Cichlidae) after Exposure to Cadmium and Zinc","volume":"66","author":"Pieterse","year":"2007","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_22","first-page":"295","article-title":"An in Vivo Study of Common Carp (Cyprinus carpio L.) Liver during Prolonged Hypoxia","volume":"2","author":"Poon","year":"2007","journal-title":"Comp. Biochem. Physiol. Part D Genom. Proteom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"200146","DOI":"10.1016\/j.cirep.2024.200146","article-title":"Hypoxia Induces Pyroptosis and Inflammation in the Liver of Fat Greenling (Hexagrammos otakii)","volume":"6","author":"Zhan","year":"2024","journal-title":"Comp. Immunol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/S0006-2952(02)01168-1","article-title":"Signal Transduction to Hypoxia-Inducible Factor 1","volume":"64","author":"Semenza","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R1079","DOI":"10.1152\/ajpregu.00626.2004","article-title":"Oxygen-Dependent Gene Expression in Fishes","volume":"288","author":"Nikinmaa","year":"2005","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.aquatox.2008.09.004","article-title":"Enhancement of Hypoxia-Induced Gene Expression in Fish Liver by the Aryl Hydrocarbon Receptor (AhR) Ligand, Benzo[a]Pyrene (BaP)","volume":"90","author":"Yu","year":"2008","journal-title":"Aquat. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1215\/S1152851704001115","article-title":"Hypoxia and the Hypoxia-Inducible-Factor Pathway in Glioma Growth Andangiogenesis","volume":"7","author":"Kaur","year":"2005","journal-title":"Neuro-Oncology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1128\/MCB.16.9.4604","article-title":"Activation of Vascular Endothelial Growth Factor Gene Transcription by Hypoxia-Inducible Factor 1","volume":"16","author":"Forsythe","year":"1996","journal-title":"Mol. Cell. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.fsi.2013.11.002","article-title":"Cloning and Immune Characterization of the C-Type Lysozyme Gene in Red-Spotted Grouper, Epinephelus akaara","volume":"36","author":"Mai","year":"2014","journal-title":"Fish Shellfish Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sun, H., Chen, F., Zheng, W., Huang, Y., Peng, H., Hao, H., and Wang, K.-J. (2024). Impact of Captivity and Natural Habitats on Gut Microbiome in Epinephelus akaara across Seasons. BMC Microbiol., 24.","DOI":"10.1186\/s12866-024-03398-y"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.aquaculture.2015.08.007","article-title":"Dietary Protein Requirement of Juvenile Red Spotted Grouper (Epinephelus akaara)","volume":"450","author":"Wang","year":"2016","journal-title":"Aquaculture"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nrg2934","article-title":"RNA Sequencing: Advances, Challenges and Opportunities","volume":"12","author":"Ozsolak","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lai, X., Zhong, Z., Lin, B., Wu, Y., Ma, Y., Zhang, C., Yang, Y., Zhang, M., Qin, W., and Fu, X. (2022). RNA-Seq and qRT-PCR Analyses Reveal the Physiological Response to Acute Hypoxia and Reoxygenation in Epinephelus coioides. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.1049776"},{"key":"ref_34","first-page":"101005","article-title":"Comparative Transcriptome Analysis Reveals Physiological Responses in Liver Tissues of Epinephelus coioides under Acute Hypoxia Stress","volume":"43","author":"Lai","year":"2022","journal-title":"Comp. Biochem. Physiol. Part D Genom. Proteom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101655","DOI":"10.1016\/j.aqrep.2023.101655","article-title":"Transcriptome and Hypoxia-Responsive Gene Expression Analyses Reveal the Physiological Reaction to Acute Hypoxia and Reoxygenation in Epinephelus coioides","volume":"31","author":"Wu","year":"2023","journal-title":"Aquac. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.anireprosci.2015.12.004","article-title":"Cloning and Pattern of Gsdf mRNA during Gonadal Development in the Protogynous Epinephelus akaara","volume":"165","author":"Chen","year":"2016","journal-title":"Anim. Reprod. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108552","DOI":"10.1016\/j.fsi.2023.108552","article-title":"Molecular Characterization, Immune Expression, and Functional Delineation of Peroxiredoxin 1 in Epinephelus akaara","volume":"133","author":"Ganeshalingam","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nclimate2595","article-title":"Linking Coasts and Seas to Address Ocean Deoxygenation","volume":"5","author":"Levin","year":"2015","journal-title":"Nat. Clim. Change"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"735903","DOI":"10.1016\/j.aquaculture.2020.735903","article-title":"Acute Hypoxia and Reoxygenation: Effect on Oxidative Stress and Hypoxia Signal Transduction in the Juvenile Yellow Catfish (Pelteobagrus fulvidraco)","volume":"531","author":"Wang","year":"2021","journal-title":"Aquaculture"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1111\/gcb.15076","article-title":"Effects of Hypoxia on the Behavior and Physiology of Kelp Forest Fishes","volume":"26","author":"Mattiasen","year":"2020","journal-title":"Glob. Change Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1007\/s10695-016-0227-1","article-title":"Effects of \u03b2-Glucan on ROS Production and Energy Metabolism in Yellow Croaker (Pseudosciaena crocea) under Acute Hypoxic Stress","volume":"42","author":"Zeng","year":"2016","journal-title":"Fish Physiol. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1469-185X.2008.00038.x","article-title":"Does Size Matter for Hypoxia Tolerance in Fish?","volume":"83","author":"Nilsson","year":"2008","journal-title":"Biol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Downie, A.T., Lefevre, S., Illing, B., Harris, J., Jarrold, M.D., McCormick, M.I., Nilsson, G.E., and Rummer, J.L. (2023). Rapid Physiological and Transcriptomic Changes Associated with Oxygen Delivery in Larval Anemonefish Suggest a Role in Adaptation to Life on Hypoxic Coral Reefs. PLoS Biol., 21.","DOI":"10.1371\/journal.pbio.3002102"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1093\/nsr\/nwz108","article-title":"Prioritizing Natural-Selection Signals from the Deep-Sequencing Genomic Data Suggests Multi-Variant Adaptation in Tibetan Highlanders","volume":"6","author":"Deng","year":"2019","journal-title":"Natl. Sci. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20140637","DOI":"10.1098\/rspb.2014.0637","article-title":"Hypoxia-Inducible Factor-1 Mediates Adaptive Developmental Plasticity of Hypoxia Tolerance in Zebrafish, Danio rerio","volume":"281","author":"Robertson","year":"2014","journal-title":"Proc. R. Soc. B Biol. Sci."},{"key":"ref_46","first-page":"300","article-title":"Molecular Cloning and Function Analysis of Insulin-like Growth Factorbinding Protein 1a in Blunt Snout Bream (Megalobrama amblycephala)","volume":"35","author":"Jie","year":"2014","journal-title":"Zool. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"90","DOI":"10.2174\/092986712803413944","article-title":"Critical Role of Hypoxia Sensor\u2014HIF-1 in VEGF Gene Activation. Implications for Angiogenesis and Tissue Injury Healing","volume":"19","author":"Ahluwalia","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kamei, H., Lu, L., Jiao, S., Li, Y., Gyrup, C., Laursen, L.S., Oxvig, C., Zhou, J., and Duan, C. (2008). Duplication and Diversification of the Hypoxia-Inducible IGFBP-1 Gene in Zebrafish. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003091"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1007\/s10695-016-0219-1","article-title":"Acute Hypoxia Up-Regulates HIF-1\u03b1 and VEGF mRNA Levels in Amazon Hypoxia-Tolerant Oscar (Astronotus ocellatus)","volume":"42","author":"Baptista","year":"2016","journal-title":"Fish Physiol. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cmet.2006.01.012","article-title":"HIF-1 Mediates Adaptation to Hypoxia by Actively Downregulating Mitochondrial Oxygen Consumption","volume":"3","author":"Papandreou","year":"2006","journal-title":"Cell Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1113\/JP280572","article-title":"Regulation of Glycolysis by the Hypoxia-inducible Factor (HIF): Implications for Cellular Physiology","volume":"599","author":"Kierans","year":"2021","journal-title":"J. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1128\/MCB.21.10.3436-3444.2001","article-title":"Transcription Factor HIF-1 Is a Necessary Mediator of the Pasteur Effect in Mammalian Cells","volume":"21","author":"Seagroves","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.bbrc.2007.07.032","article-title":"Hypoxia Increases Expression of Selective Facilitative Glucose Transporters (GLUT) and 2-Deoxy-d-Glucose Uptake in Human Adipocytes","volume":"361","author":"Wang","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sun, S., Xuan, F., Fu, H., Zhu, J., and Ge, X. (2017). Molecular Cloning and Functional Characterization of a Hexokinase from the Oriental River Prawn Macrobrachium nipponense in Response to Hypoxia. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061256"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"738605","DOI":"10.1016\/j.aquaculture.2022.738605","article-title":"The Combined Effect of Acute Hypoxic Stress and Feeding Status on the Metabolism of Yellow Catfish (Pelteobagrus fulvidraco)","volume":"560","author":"Wang","year":"2022","journal-title":"Aquaculture"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Liu, B., Wen, H., Yang, J., Li, X., Li, G., Zhang, J., Wu, S., Butts, I.A., and He, F. (2022). Hypoxia Affects HIF-1\/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (Paralichthys olivaceus). Biology, 11.","DOI":"10.3390\/biology11081233"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"131892","DOI":"10.1016\/j.ijbiomac.2024.131892","article-title":"Multi-Omics Analysis Identifies Sex-Specific Hepatic Protein-Metabolite Networks in Yellow Catfish (Pelteobagrus fulvidraco) Exposed to Chronic Hypoxia","volume":"268","author":"Zhao","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/iub.315","article-title":"The Protein Family of Glucose Transport Facilitators: It\u2019s Not Only about Glucose after All","volume":"62","author":"Augustin","year":"2010","journal-title":"IUBMB Life"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.mam.2012.07.001","article-title":"The SLC2 (GLUT) Family of Membrane Transporters","volume":"34","author":"Mueckler","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1042\/bj3290289","article-title":"Serine-294 and Threonine-295 in the Exofacial Loop Domain between Helices 7 and 8 of Glucose Transporters (GLUT) Are Involved in the Conformational Alterations during the Transport Process","volume":"329","author":"Doege","year":"1998","journal-title":"Biochem. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.bbaexp.2005.07.001","article-title":"Cloning of GLUT3 cDNA from Atlantic Cod (Gadus morhua) and Expression of GLUT1 and GLUT3 in Response to Hypoxia","volume":"1730","author":"Hall","year":"2005","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Gene Struct. Expr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/cac2.12404","article-title":"Aerobic Glycolysis Promotes Tumor Immune Evasion and Tumor Cell Stemness through the Noncanonical Function of Hexokinase 2","volume":"43","author":"He","year":"2023","journal-title":"Cancer Commun."},{"key":"ref_63","first-page":"a040535","article-title":"Glycolysis. Cold Spring Harb","volume":"13","author":"Chandel","year":"2021","journal-title":"Perspect. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Franczak, M.A., Krol, O., Harasim, G., Jedrzejewska, A., Zaffaroni, N., Granchi, C., Minutolo, F., Avan, A., Giovannetti, E., and Smolenski, R.T. (2023). Metabolic Effects of New Glucose Transporter (GLUT-1) and Lactate Dehydrogenase-A (LDH-A) Inhibitors against Chemoresistant Malignant Mesothelioma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097771"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Mishra, D., and Banerjee, D. (2019). Lactate Dehydrogenases as Metabolic Links between Tumor and Stroma in the Tumor Microenvironment. Cancers, 11.","DOI":"10.3390\/cancers11060750"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/bpa.12299","article-title":"The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor","volume":"26","author":"Valvona","year":"2016","journal-title":"Brain Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.yjmcc.2012.10.002","article-title":"Mechanism of TNF-\u03b1 Autocrine Effects in Hypoxic Cardiomyocytes: Initiated by Hypoxia Inducible Factor 1\u03b1, Presented by Exosomes","volume":"53","author":"Yu","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s12967-018-1611-7","article-title":"Unleashing Endogenous TNF-Alpha as a Cancer Immunotherapeutic","volume":"16","author":"Josephs","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Malkov, M.I., Lee, C.T., and Taylor, C.T. (2021). Regulation of the Hypoxia-Inducible Factor (HIF) by pro-Inflammatory Cytokines. Cells, 10.","DOI":"10.3390\/cells10092340"},{"key":"ref_70","first-page":"783","article-title":"PI3K\/Akt Signaling Transduction Pathway, Erythropoiesis and Glycolysis in Hypoxia (Review)","volume":"19","author":"Xie","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"533","DOI":"10.33549\/physiolres.930351","article-title":"Influence of Different Oxygen Modes on the Blood Oxygen Transport and Prooxidant-Antioxidant Status during Hepatic Ischemia\/Reperfusion","volume":"52","author":"Zinchuk","year":"2003","journal-title":"Physiol. Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Clark, E.A., and Giltiay, N.V. (2018). CD22: A Regulator of Innate and Adaptive B Cell Responses and Autoimmunity. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02235"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41419-021-03749-x","article-title":"Fas\/FasL Mediates NF-\u03baBp65\/PUMA-Modulated Hepatocytes Apoptosis via Autophagy to Drive Liver Fibrosis","volume":"12","author":"Tan","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/s41398-023-02646-5","article-title":"eIF4E Phosphorylation Mediated LPS Induced Depressive-like Behaviors via Ameliorated Neuroinflammation and Dendritic Loss","volume":"13","author":"Gong","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"30922","DOI":"10.1038\/srep30922","article-title":"Hypoxic Preconditioning Inhibits Hypoxia-Induced Apoptosis of Cardiac Progenitor Cells via the PI3K\/Akt-DNMT1-P53 Pathway","volume":"6","author":"Xu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1242\/jeb.047951","article-title":"Physiological, Behavioral and Biochemical Adaptations of Intertidal Fishes to Hypoxia","volume":"214","author":"Richards","year":"2011","journal-title":"J. Exp. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1242\/jeb.02437","article-title":"Effects of Long-Term Hypoxia on Enzymes of Carbohydrate Metabolism in the Gulf Killifish, Fundulus grandis","volume":"209","author":"Landry","year":"2006","journal-title":"J. Exp. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ren, Y., Tian, Y., Cheng, B., Liu, Y., and Yu, H. (2024). Effects of Environmental Hypoxia on Serum Hematological and Biochemical Parameters, Hypoxia-Inducible Factor (Hif) Gene Expression and HIF Pathway in Hybrid Sturgeon (Acipenser schrenckii \u2642 \u00d7 Acipenser baerii \u2640). Genes, 15.","DOI":"10.3390\/genes15060743"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.cbpc.2011.12.005","article-title":"The Effect of Hypoxia on Intermediary Metabolism and Oxidative Status in Gilthead Sea Bream (Sparus aurata) Fed on Diets Supplemented with Methionine and White Tea","volume":"155","author":"Peres","year":"2012","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"742015","DOI":"10.1016\/j.aquaculture.2024.742015","article-title":"Metabolic Responses of Small Yellow Croaker (Larimichthys polyactis) Liver to Hypoxic Stress: Insights into Glucose and Lipid Metabolism","volume":"598","author":"Wang","year":"2025","journal-title":"Aquaculture"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s10695-019-00728-0","article-title":"Involvement of the Phosphoryl Transfer Network in Gill Bioenergetic Imbalance of Pacam\u00e3 (Lophiosilurus alexandri) Subjected to Hypoxia: Notable Participation of Creatine Kinase","volume":"46","author":"Baldissera","year":"2020","journal-title":"Fish Physiol. Biochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.2337\/diabetes.51.9.2861","article-title":"Liver Pyruvate Kinase Polymorphisms Are Associated with Type 2 Diabetes in Northern European Caucasians","volume":"51","author":"Wang","year":"2002","journal-title":"Diabetes"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s10695-021-00947-4","article-title":"Histopathological, Hematological, and Biochemical Changes in High-Latitude Fish Phoxinus Lagowskii Exposed to Hypoxia","volume":"47","author":"Yang","year":"2021","journal-title":"Fish Physiol. Biochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"R1733","DOI":"10.1152\/ajpregu.00747.2004","article-title":"Regulation of Expression of Two Aquaporin Homologs in the Intestine of the European Eel: Effects of Seawater Acclimation and Cortisol Treatment","volume":"288","author":"Martinez","year":"2005","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Han, B., Meng, Y., Tian, H., Li, C., Li, Y., Gongbao, C., Fan, W., and Ma, R. (2022). Effects of Acute Hypoxic Stress on Physiological and Hepatic Metabolic Responses of Triploid Rainbow Trout (Oncorhynchus mykiss). Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.921709"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10695-008-9277-3","article-title":"Determination of Normal Values of Some Blood Serum Enzymes in Acipenser stellatus Pallas","volume":"36","author":"Shahsavani","year":"2010","journal-title":"Fish Physiol. Biochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1007\/s10695-020-00868-8","article-title":"Physiological and Metabolic Responses in Juvenile Colossoma macropomum Exposed to Hypoxia","volume":"46","author":"Favero","year":"2020","journal-title":"Fish Physiol. Biochem."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Bojarski, B., Witeska, M., and Kondera, E. (2025). Blood Biochemical Biomarkers in Fish Toxicology\u2014A Review. Animals, 15.","DOI":"10.3390\/ani15070965"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.tox.2007.11.021","article-title":"The Current State of Serum Biomarkers of Hepatotoxicity","volume":"245","author":"Ozer","year":"2008","journal-title":"Toxicology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"106502","DOI":"10.1016\/j.aquatox.2023.106502","article-title":"Hypoxia Stress Induces Hepatic Antioxidant Activity and Apoptosis, but Stimulates Immune Response and Immune-Related Gene Expression in Black Rockfish Sebastes schlegelii","volume":"258","author":"Jia","year":"2023","journal-title":"Aquat. Toxicol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"112857","DOI":"10.1016\/j.ecoenv.2021.112857","article-title":"Lead Impaired Immune Function and Tissue Integrity in Yellow Catfish (Peltobargus fulvidraco) by Mediating Oxidative Stress, Inflammatory Response and Apoptosis","volume":"226","author":"Guo","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1007\/s10499-021-00742-1","article-title":"Effects of Acute Hypoxia Stress on Hemato-Biochemical Parameters, Oxidative Resistance Ability, and Immune Responses of Hybrid Yellow Catfish (Pelteobagrus fulvidraco \u00d7 P. vachelli) Juveniles","volume":"29","author":"Dagoudo","year":"2021","journal-title":"Aquac. Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.chemosphere.2016.11.099","article-title":"Physiological Responses and Changes in Gene Expression in the Large Yellow Croaker Larimichthys crocea Following Exposure to Hypoxia","volume":"169","author":"Wang","year":"2017","journal-title":"Chemosphere"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.fsi.2015.09.013","article-title":"Stress, Antioxidant Defence and Mucosal Immune Responses of the Large Yellow Croaker Pseudosciaena crocea Challenged with Cryptocaryon irritans","volume":"47","author":"Yin","year":"2015","journal-title":"Fish Shellfish Immunol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/10\/1469\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:47:18Z","timestamp":1778561238000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/10\/1469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,10]]},"references-count":94,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ani16101469"],"URL":"https:\/\/doi.org\/10.3390\/ani16101469","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,10]]}}}