Distinct metabolic adjustments arise from acclimation to constant hypoxia and intermittent hypoxia in estuarine killifish (Fundulus heteroclitus) Available to Purchase

Many fish experience daily cycles of hypoxia in the wild, but the physiological strategies for coping with intermittent hypoxia are poorly understood. We examined how killifish adjust O₂ supply and demand during acute hypoxia, and how these responses are altered after prolonged acclimation to constant or intermittent patterns of hypoxia exposure. We acclimated killifish to normoxia (∼20 kPa O₂), constant hypoxia (2 kPa) or intermittent cycles of nocturnal hypoxia (12 h:12 h normoxia:hypoxia) for 28 days, and then compared whole-animal O₂ consumption rates (Ṁ_O2) and tissue metabolites during exposure to 12 h of hypoxia followed by reoxygenation in normoxia. Normoxia-acclimated fish experienced a pronounced 27% drop in Ṁ_O2 during acute hypoxia, and modestly increased Ṁ_O2 upon reoxygenation. They strongly recruited anaerobic metabolism during acute hypoxia, indicated by lactate accumulation in plasma, muscle, liver, brain, heart and digestive tract, as well as a transient drop in intracellular pH, and they increased hypoxia inducible factor (HIF)-1α protein abundance in muscle. Glycogen, glucose and glucose-6-phosphate levels suggested that glycogen supported brain metabolism in hypoxia, while the muscle used circulating glucose. Acclimation to constant hypoxia caused a stable ∼50% decrease in Ṁ_O2 that persisted after reoxygenation, with minimal recruitment of anaerobic metabolism, suggestive of metabolic depression. By contrast, fish acclimated to intermittent hypoxia maintained sufficient O₂ transport to support normoxic Ṁ_O2, modestly recruited lactate metabolism and increased Ṁ_O2 dramatically upon reoxygenation. Both groups of hypoxia-acclimated fish had similar glycogen, ATP, intracellular pH and HIF-1α levels as normoxic controls. We conclude that different patterns of hypoxia exposure favour distinct strategies for matching O₂ supply and O₂ demand.