Histological, biochemical and multi-omics integrative analyses provide insight into the response mechanisms of Gymnocypris eckloni to hypoxia

Hypoxia is a critical issue affecting aquatic ecosystems and organisms owing to increasingly serious global warming and water contamination. As a typical indigenous fish of the Qinghai-Tibet Plateau, Gymnocypris eckloni exhibits strong hypoxia tolerance, however, little is known about how genes, proteins and metabolites coordinate their expression and interactions in response to hypoxia. Herein, we systematically investigated the effects of acute hypoxia on G. eckloni liver using histological, biochemical and multi-omics analyses. Qualitative observations of hematoxylin and eosin, oil-red O and TUNEL staining showed that acute hypoxia could induce structural disorganization, lipid droplets formation and apoptosis. Integrated analysis of biochemical parameters, transcriptome and proteome changes revealed that G. eckloni could drive profound enhancements in anaerobic, lipid and amino acid metabolism, concomitantly activating robust endocrine and immune systems to adapt to hypoxia. The results of metabolome further supported the notion that the activation of glycolysis/gluconeogenesis, glycerolipid metabolism, amino acid metabolism and c-type lectin receptor signaling pathway was a key adaptive strategy. Besides, several key hypoxia-related gene-protein-metabolite interaction regulatory networks were identified. This study elucidates the molecular mechanisms underlying the hypoxia adaptation of G. eckloni at various levels, and contributes to the development of strategies to reduce the damage caused by hypoxia stress in fish.