Characterization of brown adipose tissue thermogenesis in the naked mole-rat (Heterocephalus glaber), a heterothermic mammal

Abstract

The naked mole-rat (NMR) is a heterothermic mammal that forms eusocial colonies consisting of one reproductive female (queen), several reproductive males, and subordinates. Despite their heterothermy, NMRs possess brown adipose tissue (BAT), which generally induces thermogenesis in cold and some non-cold environments. Previous studies suggest that NMR-BAT induces thermogenesis by cold exposure. However, detailed NMR-BAT characteristics and whether NMR-BAT thermogenesis occurs in non-cold environments are unknown. Here, we show beta-3 adrenergic receptor (ADRB3)-dependent thermogenic potential of NMR-BAT, which contributes to thermogenesis in the isolated queen in non-cold environments (30 °C). NMR-BAT expressed several brown adipocyte marker genes and showed noradrenaline-dependent thermogenic activity in vitro and in vivo. Although our ADRB3 inhibition experiments revealed that NMR-BAT thermogenesis slightly delays the decrease in body temperature in a cold environment (20 °C), it was insufficient to prevent the decrease in the body temperatures. Even at 30 °C, NMRs are known to prevent the decrease of and maintain their body temperature by heat-sharing behaviors within the colony. However, isolated NMRs maintained their body temperature at the same level as when they are in the colony. Interestingly, we found that queens, but not subordinates, induce BAT thermogenesis in this condition. Our research provides novel insights into NMR thermoregulation.

Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain

“…The dissected SVZ was dissociated by gentle pipetting after treatment with trypsin and hyaluronidase, suspended in NSC culture medium supplemented with B27, bFGF, and EGF, as previously used in other species [ 31 ], and cultured in neurosphere culture conditions. The NMR is a unique heterothermic animal with a low body temperature and its cells are vulnerable to culture in normoxia [ 17 , 32 ]; therefore, the cells were cultured at 32°C and in 3% O 2 . Neurospheres formed after 15 days of cultivation (Fig.…”

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

“…In most small mammals, BAT thermogenesis is an energy-intensive process that can drastically impact whole-body energy homeostasis 25 , 41 . Previous studies indicate the existence of functional iBAT in naked mole-rats 16 , 18 , 42 . Furthermore, activation of BAT in naked mole-rats greatly increases whole-animal oxygen consumption, and this increase explains most of the increases in whole-body oxygen consumption in naked mole-rats under these conditions 42 – 44 .…”

“…Naked mole-rats meet the definition of heterotherms because they are weakly capable of thermogenesis but are generally not very efficient thermoregulators 14 , 16 . This is primarily due to their lack of insulating fur and fat 17 , which allows for rapid loss of heat through convective mechanisms.…”

“…Activation of UCP1 uncouples mitochondrial respiration from ATP-synthesis, resulting in heat generation through futile cycling of the electron transport chain (ETC) 23 , 24 . Importantly, naked mole-rats express functional BAT 16 ; however, no study has directly examined thermogenic adaptations to hypoxia or the underlying mechanisms in this species. Given the high cost of thermoregulation (particularly for a small and naked rodent) and the requisite need to lower metabolic demand in hypoxia, such an investigation is of pressing interest in the study of ecophysiological adaptations to life in hypoxia in this fascinating species.…”

Is brown adipose tissue a new target for obesity therapy?

“…Мыши, лишенные БЖТ, склонны к ожирению, а мыши с повышенной активностью БЖТ были защищены от негативных метаболических эффектов высококалорийной диеты [8]. Интересен тот факт, что самые долгоживущие мелкие грызуны -голые землекопы (продолжительность жизни до 32 лет) имеют большое количество и высокую активность БЖТ [9].…”