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Short-and long-term hypoxia induces sex-specific metabolic reprogramming in Trachinotus blochii

ABSTRACT: The golden pompano (Trachinotus blochii), a key marine aquaculture species, frequently encounters hypoxic stress under intensive farming conditions, which has become a critical environmental factor constraining its physiological functions and aquaculture productivity. Given the species pronounced sensitivity to hypoxia, this study systematically investigated the metabolic regulatory mechanisms of T. blochii under varying hypoxic exposure durations through short-term (24-hour) and long-term (14-day) hypoxic stress experiments. The results revealed that under acute hypoxia, the lactate (LA) concentration and activities of glycolytic key enzymes—including lactate dehydrogenase (LDH), hexokinase (HK), pyruvate kinase (PK), and phosphofructokinase (PFK)—were significantly upregulated, indicating rapid energy supply via anaerobic glycolysis activation. Notably, during the short-term hypoxic adaptation phase, alongside sustained increases in LA levels and LDH/PFK activities, lipid metabolism indicators exhibited marked alterations: triglyceride (TG) and non-esterified fatty acid (NEFA) contents lipase (LPS) activity increased, suggesting a metabolic shift from exclusive glycolysis to coordinated glucose-lipid utilization. Transcriptome sequencing analysis further revealed that the short-term hypoxia group exhibited significant enrichment of differentially expressed genes (DEGs) in the glycolysis/gluconeogenesis pathway. Meanwhile, DEGs between males and females in the short-term hypoxia group were mainly enriched in the taurine and hypochlorous acid metabolism pathways, while DEGs in the long-term hypoxia group were co-enriched in the glycolysis/gluconeogenesis and fat digestion/absorption pathways. Long-term hypoxia exposure resulted in gender-specific gene expression differences primarily concentrated in the pantothenic acid and coenzyme A biosynthesis pathways. This study elucidates that T. blochii achieves hypoxic adaptation through metabolic reprogramming: under short-term hypoxia conditions, it prioritizes rapid glucose mobilization for emergency energy supply, with females exhibiting enhanced antioxidant defense capabilities. Under long-term hypoxia conditions, it adopts a synergistic glucose-lipid metabolism enhancement strategy, and both sexes modulate energy metabolism to cope with hypoxia.

ORGANISM(S): Trachinotus blochii

PROVIDER: GSE309304 | GEO | 2026/10/01

REPOSITORIES: GEO

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Project description:Oxygen fluctuation during tissue remodeling imposes a major metabolic challenge in human tumors. Stem-like tumor cells in glioblastomas are believed to possess extraordinary metabolic flexibility, enabling them to initiate growth even under non-permissive conditions. To identify adaptive response mechanism, we compared the effects of acute and chronic hypoxia versus oxygenation on stem-like glioblastoma (GS) cells. GS cell lines were established and propagated either under normoxia (21% O2) or hypoxia (1% O2) and subsequently exposed to acute normoxia or hypoxia, respectively. Gene expression profiling revealed that acute hypoxia predominantly induced metabolic pathways and cell cycle arrest, whereas chronic hypoxia activated neurodevelopmental processes. In particular, we found increased expression of glycolytic enzymes, especially of the preparatory phase of glycolysis, under acute hypoxia, whereas pentose phosphate pathway (PPP) enzymes were downregulated. The opposite was found for acute oxygenation of hypoxic GS cells. Findings were confirmed by qPCR and immunoblot analyses. Despite downregulation by hypoxia, expression of PPP enzymes is increased in GBMs compared to normal brain, whereas expression of hypoxia-inducible enzymes of the parallel preparatory phase of glycolysis is decreased. Immunohistochemistry revealed strong staining for PPP enzymes in the bulk of GBM tissue, especially in highly proliferative areas, but not in pseudopalisading (hypoxic) cells. Glycolytic enzymes displayed an inverse pattern. Mass spectrometric analysis using [1,2-13C2]-D-glucose showed reduced glucose flux through the PPP under hypoxia in favor of flux through glycolysis. Acute and chronic hypoxia increased cell migration but reduced proliferation, whereas normoxia had opposite effects. Our findings extend Warburg’s observations by showing that in most tumor cells the PPP, which supplies metabolites for biomass production, is favored over the parallel preparatory phase of glycolysis, but is suppressed under acute severe hypoxia, causing a switch to direct glycolysis to protect against hypoxic stress.

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Short-and long-term hypoxia induces sex-specific metabolic reprogramming in Trachinotus blochii

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