Naked mole-rat brown fat thermogenesis is diminished during hypoxia through a rapid decrease in UCP1

Naked mole-rats are among the most hypoxia-tolerant mammals. During hypoxia, their body temperature (T-b) decreases via unknown mechanisms to conserve energy. In small mammals, non-shivering thermogenesis in brown adipose tissue (BAT) is critical to T-b regulation; therefore, we hypothesize that hypoxia decreases naked mole-rat BAT thermogenesis. To test this, we measure changes in T-b during normoxia and hypoxia (7% O-2; 1-3 h). We report that interscapular thermogenesis is high in normoxia but ceases during hypoxia, and T-b decreases. Furthermore, in BAT from animals treated in hypoxia, UCP1 and mitochondrial complexes I-V protein expression rapidly decrease, while mitochondria undergo fission, and apoptosis and mitophagy are inhibited. Finally, UCP1 expression decreases in hypoxia in three other social African mole-rat species, but not a solitary species. These findings suggest that the ability to rapidly down-regulate thermogenesis to conserve oxygen in hypoxia may have evolved preferentially in social species. Naked mole-rats are hypoxia-tolerant mammals, and during hypoxia their body temperature decreases via unknown mechanisms. Here the authors report that the hypoxia-induced body temperature decrease in naked mole rats occurs through decreased brown adipose tissue thermogenesis via decreases in a key thermogenic mitochondrial protein: UCP1.

Automated summary

Naked mole-rats, among the most hypoxia-tolerant mammals, decrease their body temperature in low oxygen conditions through reduced brown adipose tissue thermogenesis, driven by decreases in the key thermogenic mitochondrial protein UCP1. This down-regulation of thermogenesis in hypoxia is associated with mitochondrial fission, inhibited apoptosis and mitophagy in brown adipose tissue, suggesting an evolved preference for rapid energy conservation in social species under low oxygen conditions.