Tissue specific metabolite responses of the liver, muscle and heart of the Pacific hagfish, (Eptatretus stoutii) to prolonged anoxia exposure.

Pacific hagfish (Eptatretus stoutii) can tolerate up to 36 h of anoxia. Characteristics that enable this include a low constitutive metabolism as well as moderate hypometabolism during anoxia exposure. However, additional stressors manifest during anoxia and reoxygenation including the accumulation of metabolic products and mitochondrial dysfunction upon reoxygenation. We investigated these by examining the metabolite responses of hagfish exposed to 6 h and 24 h of anoxia. Metabolites of interest were lactate, an anaerobic product, and succinate, a driver of mitochondrial dysfunction in reoxygenation. We quantified metabolites in three tissues; the systemic heart, white muscle, and liver. We found that six hours of anoxia caused minimal change to the metabolites with no significant accumulation of lactate or succinate compared to control fish. Twenty-four hours of anoxia did have a larger impact on metabolite balance. Lactate concentrations increased by 36.3-fold, 2.1-fold, and 17.1-fold in the systemic heart, white muscle, and liver respectively. Succinate was 9.0-fold higher in the systemic heart and 3.5-fold higher in the white muscle. This accumulation is comparable to other anoxia-tolerant species that may reduce the potential for mitochondrial dysfunction upon reoxygenation. Additional metabolite changes were related to amino acid balance and energy availability, and the heart was the most affected organ. Finally, we identified three novel metabolites more common to invertebrates, N-methyl taurine, homarine, and zooanemonin. In conclusion, Pacific hagfish demonstrated high lactate and low succinate accumulation following 24 h of anoxia. This anoxia response resembles that of the anoxia-tolerant freshwater turtles more than that of the crucian carp.