Transcriptional and epigenetic responses to acute hypoxia exposure in rainbow trout (Oncorhynchus mykiss)

Abstract

Rainbow trout, which are comparatively intolerant to low oxygen, face increasing hypoxic events. This study investigated their metabolic and molecular responses to acute hypoxia and investigated whether O₂-dependent epigenetic marks mediate these responses. Adult rainbow trout were exposed to normoxia (10.5 mg/L dissolved oxygen (DO)), 50 % hypoxia (5.25 mg/L DO) and 25 % oxygen saturation (2.61 mg/L DO) for 4 h. Plasma metabolites and cortisol were measured, as were transcripts of hypoxia-responsive genes involved in oxygen sensing, glucose/lactate metabolism, and lipid metabolism in liver, white/red muscle, and adipose tissue. Global DNA methylation and promoter-specific histone modifications (H3K4me3) were profiled in the liver. Lactate and, to a lesser extent, glucose concentrations increased, while lipid metabolites remained unchanged. The stress hormone cortisol was significantly elevated. At the tissue level, the liver was most sensitive to hypoxia and exhibited the most pronounced transcriptional changes. Hepatic gene transcripts involved in lactate transport and glycolysis increased at 50 % oxygen saturation, while gene transcripts involved in gluconeogenesis and fatty acid import and synthesis were induced at 25 % oxygen saturation. Hepatic global DNA methylation remained unchanged, but promoter-specific H3K4me3 modifications were observed for the phosphoenolpyruvate carboxykinase 1 gene. However, no direct correlation between pck1 H3K4me3 promoter occupancy and pck1 expression was evident, suggesting other transcriptional control mechanisms. This research provides insights into the tissue-specific metabolic responses and epigenetic mechanisms in rainbow trout under acute hypoxia, paving the way for comparative studies probing the role of oxygen-sensitive epigenetic markers in transcriptional responses to hypoxia in other fish species.