Do naked mole rats accumulate a metabolic acidosis or an oxygen debt in severe hypoxia?

Abstract

In severe hypoxia, most vertebrates increase anaerobic energy production, which results in the development of a metabolic acidosis and an O2 debt that must be repaid during reoxygenation. Naked mole rats (NMRs) are among the most hypoxia-tolerant mammals, capable of drastically reducing their metabolic rate in acute hypoxia; while staying active and alert. We hypothesized that a key component of remaining active is an increased reliance on anaerobic metabolism during severe hypoxia. To test this hypothesis, we exposed NMRs to progressive reductions in inspired O2 (9 to 3% O2) followed by reoxygenation (21% O2) and measured breathing frequency, heart rate, behavioural activity, body temperature, metabolic rate, and also metabolic substrates and pH in blood and tissues. We found that NMRs exhibit robust metabolic rate depression in acute hypoxia, accompanied by declines in all physiological and behavioural variables examined. However, blood and tissue pH were unchanged and tissue [ATP] and [phosphocreatine] were maintained. Naked mole rats increased their reliance on carbohydrates in hypoxia, and glucose was mobilized from the liver to the blood. Upon reoxygenation NMRs entered into a coma-like state for∼15-20 mins during which metabolic rate was negligible and body temperature remained suppressed. However, an imbalance in the rates at which V̇O2 and V̇CO2 returned to normoxic levels during reoxygenation hint at the possibility that NMRs do utilize anaerobic metabolism during hypoxia but have a tissue and/or blood buffering capacity that mask typical markers of metabolic acidosis, and prioritize the synthesis of glucose from lactate during recovery.