Hypoxia and Thermogenesis Constrain Peak V<scp>o</scp>₂ in Exercising Naked Mole Rats

AbstractHypoxia-tolerant naked mole rats (NMRs) depress metabolic rate >85% in severe hypoxia and switch from mixed lipids/carbohydrates to total carbohydrate-fueled metabolism. Previous experiments have studied resting animals, but how exercising NMRs balance hypoxic hypometabolism with thermogenic and activity-related demands is unknown. Therefore, we explored how interactions between hypoxia and intense exercise impact metabolic rate (oxygen consumption rate [V̇o₂]), aerobic scope, and fuel usage in normoxia or hypoxia (7% O₂) and at 22°C or 30°C. We found that hypoxia had the largest impact on both V̇o₂ and peak V̇o₂ in either temperature and both in stationary-wheel conditions and during forced exercise (animals made to run at their maximum sustainable rate). In hypoxia, exercising V̇o₂ and peak V̇o₂ were not elevated from stationary-wheel conditions, indicating that hypoxia constrains the metabolic scope available for intense exercise. Conversely, metabolic rate was not impacted by temperature in hypoxia. Finally, hypoxia, but not exercise or experimental temperature, drove a shift in fuel use toward carbohydrate metabolism. Together, our findings indicate that environmental hypoxia is the primary determinant of metabolic fuel use and the key limiter of V̇o₂ in exercising NMRs. We conclude that hypoxic hypometabolism is prioritized over thermoregulatory and behavioral demands in this species. This relationship likely supports the ecophysiology of this species: NMR burrows are presumed to be warmest and most hypoxic in densely populated nests where animals tend to be sedentary but cooler and less hypoxic in distant burrow regions where animals undertake energetically intense tasks, such as tunnel expansion and foraging behaviors.