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

Hang Cheng, Rajaa Sebaa, Nikita Malholtra, Baptiste Lacoste, Ziyad El Hankouri, Alexia Kirby, Nigel C. Bennett, Barry Jaarsveld, Daniel W. Hart, Glenn J. Tattersall, Mary-Ellen Harper () and Matthew E. Pamenter ()
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Hang Cheng: University of Ottawa
Rajaa Sebaa: University of Ottawa
Nikita Malholtra: University of Ottawa
Baptiste Lacoste: University of Ottawa
Ziyad El Hankouri: University of Ottawa
Alexia Kirby: University of Ottawa
Nigel C. Bennett: University of Pretoria
Barry Jaarsveld: University of Pretoria
Daniel W. Hart: University of Pretoria
Glenn J. Tattersall: Brock University
Mary-Ellen Harper: University of Ottawa
Matthew E. Pamenter: University of Ottawa

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Naked mole-rats are among the most hypoxia-tolerant mammals. During hypoxia, their body temperature (Tb) decreases via unknown mechanisms to conserve energy. In small mammals, non-shivering thermogenesis in brown adipose tissue (BAT) is critical to Tb regulation; therefore, we hypothesize that hypoxia decreases naked mole-rat BAT thermogenesis. To test this, we measure changes in Tb during normoxia and hypoxia (7% O2; 1–3 h). We report that interscapular thermogenesis is high in normoxia but ceases during hypoxia, and Tb 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.

Date: 2021
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DOI: 10.1038/s41467-021-27170-2

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