Naked mole-rats rapidly decrease UCP1 in hypoxia

/ gtattersall

I’m happy to report on a paper from Matt Pamenter’s lab (U Ottawa) that has just been published in Nature Communications. Matt and colleagues teamed up to examine how naked mole rats show a remarkable capacity to rapidly down-regulate UCP1 levels in their brown fat. It might come as a bit of a surprise to some to hear that naked mole-rats even have functional UCP1, since they are often described as “poikilothermic” mammals, not capable of producing heat. This is actually not entirely accurate, as can be seen in thermal images of naked mole-rats (Figure 1 below from Cheng et al 2021), they have a substantial band of heat within their shoulder region, where the brown fat lies.

Figure 1. Thermogenesis ceases in acute hypoxia and body temperature drops to ambient levels.

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 hypothesized 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.

This work was a team effort, lead by Dr. Matt Pamenter’s lab at U Ottawa and Dr. Mary-Ellen Harper (U Ottawa), and included colleagues from the University of Pretoria, and University of Shaqra, Saudi Arabia, and myself (Brock University).

Here is a link to the paper.

https://rdcu.be/cBR7d

Citation

Cheng, H, Rebaa, R, Malholtra, N, Lacost, B, El Hankouri, Z, Kirby, A, Bennett, NC, van Jaarsveld, B, Hart, DW, Tattersall, GJ, Harper, M-E, and Pamenter, ME. 2021. Naked mole-rat brown fat thermogenesis is diminished during hypoxia through a rapid decrease in UCP1. Nature Communications, 12: 6801. https://doi.org/10.1038/s41467-021-27170-2