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

裸鼹鼠棕色脂肪的产热作用在缺氧期间因 UCP1 的快速下降而减弱

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作者:Hang Cheng, Rajaa Sebaa, Nikita Malholtra, Baptiste Lacoste, Ziyad El Hankouri, Alexia Kirby, Nigel C Bennett, Barry van Jaarsveld, Daniel W Hart, Glenn J Tattersall, Mary-Ellen Harper #, Matthew E Pamenter #

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.

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