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

Hang Cheng1, Rajaa Sebaa2,3,4, Nikita Malholtra1

  • 1Department of Biology, University of Ottawa, Ottawa, ON, Canada.

Nature Communications
|November 24, 2021
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Summary
This summary is machine-generated.

Hypoxia lowers body temperature in naked mole-rats by stopping brown adipose tissue (BAT) thermogenesis. This oxygen-conserving mechanism may have evolved in social African mole-rat species.

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Area of Science:

  • Physiology
  • Mammalian Biology
  • Comparative Biology

Background:

  • Naked mole-rats exhibit remarkable hypoxia tolerance.
  • Body temperature regulation during hypoxia in mammals is not fully understood.
  • Non-shivering thermogenesis in brown adipose tissue (BAT) is crucial for thermoregulation in small mammals.

Purpose of the Study:

  • To investigate the role of BAT thermogenesis in naked mole-rat body temperature (Tb) regulation during hypoxia.
  • To test the hypothesis that hypoxia decreases BAT thermogenesis in naked mole-rats.

Main Methods:

  • Measurements of Tb and interscapular thermogenesis in naked mole-rats under normoxia and hypoxia (7% O2).
  • Analysis of protein expression (UCP1, mitochondrial complexes I-V) in BAT after hypoxic exposure.
  • Assessment of mitochondrial morphology (fission/fusion) and cellular processes (apoptosis, mitophagy) in BAT.
  • Comparative analysis of UCP1 expression during hypoxia in different African mole-rat species.

Main Results:

  • Interscapular thermogenesis, high during normoxia, ceased during hypoxia, correlating with a decrease in Tb.
  • Hypoxia exposure led to rapid decreases in UCP1 and mitochondrial complex protein expression in BAT.
  • Mitochondria in BAT underwent fission, while apoptosis and mitophagy were inhibited under hypoxic conditions.
  • UCP1 expression decreased in hypoxia in three social mole-rat species but not in a solitary species.

Conclusions:

  • Naked mole-rats down-regulate BAT thermogenesis to conserve oxygen during hypoxia.
  • The observed changes in BAT suggest a coordinated response to reduce metabolic rate and energy expenditure.
  • The preferential down-regulation of thermogenesis in social mole-rat species indicates an evolutionary adaptation linked to sociality and hypoxia tolerance.