Severe acute hypoxia upregulates anaerobic metabolism in non-reproductive but not queen naked mole-rats

Most vertebrates upregulate anaerobic metabolism in severe hypoxia, which results in metabolic acidosis that must be resolved during reoxygenation. Naked mole-rats (NMRs) are hypoxia-tolerant mammals and drastically reduce their metabolic rate while maintaining systemic pH homeostasis during acute hypoxia. Whether NMRs employ anaerobic metabolism in hypoxia is currently debated. Given the robust systemic hypoxic hypometabolism of this species, we hypothesized that anaerobic metabolism is recruited on a tissue-specific basis that varies between developmental stages and colony caste position. To test this, we treated subordinate juvenile and adult, and breeding (queen) NMRs in normoxia (21% O2) or hypoxia (3% O2) for 1 h, and then measured blood lactate, glycolytic enzyme activity, and the expression of genes that encode for enzymes involved in glycogen and glucose metabolism, and lactate transport. We found that (1) blood lactate levels increase similarly during hypoxia across developmental stages and castes, but that (2) glycolytic activity increased or remained stable in subordinates and juveniles but was unchanged or reduced in queens; (3) MCT4 gene expression decreased markedly in subordinate and juvenile brain and increased in muscle and kidney, but was unchanged in queens; and (4) the expression of genes associated with glycogenolysis and gluconeogenesis varied across tissues in subordinates/juveniles with some markers being down or upregulated or unchanged, but were always unchanged or downregulated queens. Taken together, our results suggest that hypoxia upregulates glycolysis and glycogen mobilization in subordinates and juveniles, but not in queens.