Torpor patterns, arousal rates, and temporal organization of torpor entry in wildtype and UCP1-ablated mice

Abstract

In eutherian mammals, uncoupling protein 1 (UCP1) mediated non-shivering thermogenesis from brown adipose tissue (BAT) provides a mechanism through which arousal from torpor and hibernation is facilitated. In order to directly assess the magnitude by which the presence or absence of UCP1 affects torpor patterns, rewarming and arousal rates within one species we compared fasting induced torpor in wildtype (UCP1(+/+)) and UCP1-ablated mice (UCP(-/-)). Torpor was induced by depriving mice of food for up to 48 h and by a reduction of ambient temperature (T (a)) from 30 to 18°C at four different time points after 18, 24, 30 and 36 h of food deprivation. In most cases, torpor bouts occurred within 20 min after the switch in ambient temperature (30-18°C). Torpor bouts expressed during the light phase lasted 3-6 h while significantly longer bouts (up to 16 h) were observed when mice entered torpor during the dark phase. The degree of hypometabolism (5-22 ml h(-1)) and hypothermia (19.5-26.7°C) was comparable in wildtype and UCP1-ablated mice, and both genotypes were able to regain normothermia. In contrast to wildtype mice, UCP1-ablated mice did not display multiple torpor bouts per day and their peak rewarming rates from torpor were reduced by 50% (UCP1(+/+): 0.24 ± 0.08°C min(-1); UCP1(-/-): 0.12 ± 0.04°C min(-1)). UCP1-ablated mice therefore took significantly longer to rewarm from 25 to 32°C (39 vs. 70 min) and required 60% more energy for this process. Our results demonstrate the energetic benefit of functional BAT for rapid arousal from torpor. They also suggest that torpor entry and maintenance may be dependent on endogenous rhythms.

Increased thermogenic capacity of brown adipose tissue under low temperature and its contribution to arousal from hibernation in Syrian hamsters

“…Although a UCP1-independent compensatory thermogenic mechanism mediated by sympathetic ␤ 3 -receptors has been reported (26,36), it is known that UCP1 can mediate adaptive NST potently and effectively in response to cold (8). Conclusive findings demonstrating the necessity of BAT during the arousal phase of hibernation was not acquired in this study, but the present results strongly imply that BAT function is indispensable for warming of the body in the early phase of arousal.…”

“…This importance of BAT functions may be conclusively revealed in the not-so-distant future by investigations using techniques such as gene knock out (26) and reversible and highly selective blocking of BAT/UCP1 function. Analysis of the regulation mechanism of BAT thermogenesis at the molecular level may also contribute to the investigation of this hibernation mechanism.…”

“…The development of a reversible and highly selective method of blocking BAT/UCP1 function is required to conclusively determine whether BAT function is required. Genetic ablation of UCP1 in hamsters may be a candidate for such a method (26).…”

“…Recently, the existence of functional BAT in adults has been confirmed by using state of the art methods (40,42). Despite both the difficulty of BAT detection in obese persons (39) and the occurrence of compensatory NST in genetically BAT-ablated mice (26), it is suspected that BAT still remains important in nonhibernators, including humans, and it is estimated that Ͼ 50% of NST in response to cold stimulation is caused by BAT. In the hiber- Values are means Ϯ SD.…”

Nature's fat-burning machine: brown adipose tissue in a hibernating mammal

“…Because shivering cannot occur when the animal is in torpor, BATderived heat is essential for initiating arousal. Indeed, BAT thermogenesis reduces the energetic costs of the arousal by 60% by accelerating the rewarming process (Oelkrug et al, 2011). Moreover, the highest rate of BAT activity occurs during IBAs when heat production occurs very quickly.…”