Depression of mitochondrial respiration during daily torpor of the Djungarian hamster,Phodopus sungorus,is specific for liver and correlates with body temperature

Small mammals actively decrease metabolism during daily torpor and hibernation to save energy. Increasing evidence suggests depression of mitochondrial respiration during daily torpor of the Djungarian hamster but tissue-specificity and relation to torpor depth is unknown. We first confirmed a previous study by Brown and colleagues reporting on the depressed substrate oxidation in isolated liver mitochondria of the Djungarian hamster (Phodopus sungorus) during daily torpor. Next, we show that mitochondrial respiration is not depressed in kidneys, skeletal muscle and heart. In liver mitochondria, we found that state 3 and state 4 respirations correlate with body temperature, suggesting inhibition related to torpor depth and to metabolic rate. We conclude that molecular events leading to depression of mitochondrial respiration during daily torpor are specific to liver and linked to a decrease in body temperature. Different tissue-specificity of mitochondrial depression may assist to compare and identify the molecular nature of mitochondrial alterations during torpor.     

Effect of low-quality diet on torpor frequency and depth in the pichi Zaedyus pichiy (Xenarthra,Dasypodidae), a South American armadillo

Daily torpor is a physiological adaptation that allows mammals to cope with energetic challenges associated with unpredictable periods of food shortage. We experimentally tested whether food quality influences torpor frequency and depth in the pichi (Zaedyus pichiy), a small, opportunistically omnivorous armadillo endemic to arid and semi-arid habitats of southern South America. We recorded body temperature (T_sc) changes in 10 semi-captive, adult female pichis using dataloggers implanted subcutaneously during periods of 21 days. All individuals entered spontaneous daily torpor, but those receiving a low-quality diet had significantly lower daily mean and minimum T_sc, spent more time at T_sc below their individual lower limit of normothermia, and had a higher Heterothermy Index than controls. Five individuals entered prolonged torpor bouts lasting more than 24 h, two of them repeatedly. Nine out of ten prolonged torpor bouts occurred in individuals feeding on a low-quality diet, suggesting that pichis are able to enter prolonged periods of torpor during severe environmental stress. In combination with their ability to hibernate and to respond to a reduced insect abundance by ingesting other food items, this physiological adaptation allows pichis to better cope with food shortages and a more extreme climate than other armadillos. It may explain why Z. pichiy naturally occurs farther south than any other armadillo species.     

Daily torpor and hibernation in birds and mammals

Many birds and mammals drastically reduce their energy expenditure during times of cold exposure, food shortage, or drought, by temporarily abandoning euthermia, i.e. the maintenance of high body temperatures. Traditionally, two different types of heterothermy, i.e. hypometabolic states associated with low body temperature (torpor), have been distinguished: daily torpor, which lasts less than 24 h and is accompanied by continued foraging, versus hibernation, with torpor bouts lasting consecutive days to several weeks in animals that usually do not forage but rely on energy stores, either food caches or body energy reserves. This classification of torpor types has been challenged, suggesting that these phenotypes may merely represent extremes in a continuum of traits. Here, we investigate whether variables of torpor in 214 species (43 birds and 171 mammals) form a continuum or a bimodal distribution. We use Gaussian‐mixture cluster analysis as well as phylogenetically informed regressions to quantitatively assess the distinction between hibernation and daily torpor and to evaluate the impact of body mass and geographical distribution of species on torpor traits. Cluster analysis clearly confirmed the classical distinction between daily torpor and hibernation. Overall, heterothermic endotherms tend to be small; hibernators are significantly heavier than daily heterotherms and also are distributed at higher average latitudes (～35°) than daily heterotherms (～25°). Variables of torpor for an average 30 g heterotherm differed significantly between daily heterotherms and hibernators. Average maximum torpor bout duration was >30‐fold longer, and mean torpor bout duration >25‐fold longer in hibernators. Mean minimum body temperature differed by ～13°C, and the mean minimum torpor metabolic rate was ～35% of the basal metabolic rate (BMR) in daily heterotherms but only 6% of BMR in hibernators. Consequently, our analysis strongly supports the view that hibernators and daily heterotherms are functionally distinct groups that probably have been subject to disruptive selection. Arguably, the primary physiological difference between daily torpor and hibernation, which leads to a variety of derived further distinct characteristics, is the temporal control of entry into and arousal from torpor, which is governed by the circadian clock in daily heterotherms, but apparently not in hibernators.     

Cool birds: first evidence of energy-saving nocturnal torpor in free-living common swifts Apus apus resting in their nests

Daily torpor is a means of saving energy by controlled lowering of the metabolic rate (MR) during resting, usually coupled with a decrease in body temperature. We studied nocturnal daily torpor under natural conditions in free-living common swifts Apus apus resting in their nests as a family using two non-invasive approaches. First, we monitored nest temperature (T_nest) in up to 50 occupied nests per breeding season in 2010–2015. Drops in T_nest were the first indication of torpor. Among 16 673 observations, we detected 423 events of substantial drops in T_nest of on average 8.6°C. Second, we measured MR of the families inside nest-boxes prepared for calorimetric measurements during cold periods in the breeding seasons of 2017 and 2018. We measured oxygen consumption and carbon dioxide production using a mobile indirect respirometer and calculated the percentage reduction in MR. During six torpor events observed, MR was gradually reduced by on average 56% from the reference value followed by a decrease in T_nest of on average 7.6°C. By contrast, MR only decreased by about 33% on nights without torpor. Our field data gave an indication of daily torpor, which is used as a strategy for energy saving in free-living common swifts.     

From slow waves to sleep homeostasis: new perspectives

EEG slow waves are the epitome of deep nonREM sleep. The level of slow-wave activity (SWA; defined as spectral power in the 0.5-4.5 Hz band) in the initial part of sleep is determined by prior sleep and waking, and thereby represents a marker of a homeostatic sleep regulating process (Process S). Models based on SWA were successful in simulating sleep architecture in a variety of experimental protocols. SWA is an exceptional sleep variable in that it is little influenced by circadian phase and variations of the photoperiod. There is recent evidence that it is not waking per se but the absence of sleep, which engenders a rise in sleep propensity. Thus animals emerging from the hypometabolic states of hibernation or daily torpor exhibit an increase in SWA akin to sleep deprivation. Recent human studies showed SWA to be a marker of a local, use-dependent facet of sleep. Selective activation of specific cortical areas during waking enhanced SWA over the activated region during sleep. A frontal predominance of power in the 2-Hz band was documented in the initial part of a normal sleep episode. Sleep homeostasis may be a valuable concept for exploring the evolutionary origin of sleep. Thus 'rest homeostasis' has been demonstrated in invertebrate species, and the search for homologies of rest and sleep on a molecular genetic level has begun. Conceptualizing and characterizing sleep as a regulated process may eventually shed light on its function.     

Induction of Antioxidant and Heat Shock Protein Responses During Torpor in the Gray Mouse Lemur,Microcebus murinus

A natural tolerance of various environmental stresses is typically supported by various cytoprotective mechanisms that protect macromolecules and promote extended viability. Among these are antioxidant defenses that help to limit damage from reactive oxygen species and chaperones that help to minimize protein misfolding or unfolding under stress conditions. To understand the molecular mechanisms that act to protect cells during primate torpor, the present study characterizes antioxidant and heat shock protein(HSP) responses in various organs of control(aroused)and torpid gray mouse lemurs, Microcebus murinus. Protein expression of HSP70 and HSP90 a was elevated to 1.26 and 1.49 fold, respectively, in brown adipose tissue during torpor as compared with control animals, whereas HSP60 in liver of torpid animals was 1.15 fold of that in control(P 0.05). Among antioxidant enzymes, protein levels of thioredoxin 1 were elevated to 2.19 fold in white adipose tissue during torpor, whereas Cu–Zn superoxide dismutase 1 levels rose to 1.1 fold in skeletal muscle(P 0.05). Additionally, total antioxidant capacity was increased to 1.6 fold in liver during torpor(P 0.05), while remaining unchanged in the five other tissues. Overall, our data suggest that antioxidant and HSP responses are modified in a tissue-specific manner during daily torpor in gray mouse lemurs. Furthermore, our data also show that cytoprotective strategies employed during primate torpor are distinct from the strategies in rodent hibernation as reported in previous studies.     

Thyroid hormone status affects expression of daily torpor and gene transcription in Djungarian hamsters (Phodopus sungorus)

Thyroid hormones (TH) play a key role in regulation of seasonal as well as acute changes in metabolism. Djungarian hamsters (Phodopus sungorus) adapt to winter by multiple changes in behaviour and physiology including spontaneous daily torpor, a state of hypometabolism and hypothermia. We investigated effects of systemic TH administration and ablation on the torpor behaviour in Djungarian hamsters adapted to short photoperiod. Hyperthyroidism was induced by giving T4 or T3 and hypothyroidism by giving methimazole (MMI) and sodium perchlorate via drinking water. T3 treatment increased water, food intake and body mass, whereas MMI had the opposite effect. Continuous recording of body temperature revealed that low T3 serum concentrations increased torpor incidence, lowered T_b and duration, whereas high T3 serum concentrations inhibited torpor expression. Gene expression of deiodinases (dio) and uncoupling proteins (ucp) were analysed by qPCR in hypothalamus, brown adipose tissue (BAT) and skeletal muscle. Expression of dio2, the enzyme generating T3 by deiodination of T4, and ucps, involved in thermoregulation, indicated a tissue specific response to treatment. Torpor per se decreased dio2 expression irrespective of treatment or tissue, suggesting low intracellular T3 concentrations during torpor. Down regulation of ucp1 and ucp3 during torpor might be a factor for the inhibition of BAT thermogenesis. Hypothalamic gene expression of neuropeptide Y, propopiomelanocortin and somatostatin, involved in feeding behaviour and energy balance, were not affected by treatment. Taken together our data indicate a strong effect of thyroid hormones on torpor, suggesting that lowered intracellular T3 concentrations in peripheral tissues promote torpor.     

Confirmation of pleisiomorphic daily torpor in mammals: the round-eared elephant shrew Macroscelides proboscideus (Macroscelidea)

The characteristics of daily torpor were measured in the round-eared elephant shrew Macroscelides proboscideus (Macroscelidea) in response to ambient temperature and food deprivation. Elephant shrews are an ancient mammal order within a superordinal African clade including hyraxes, elephants, dugongs and the aardvark. M. proboscideus only employed torpor when deprived of food; torpor did not occur under an ad libitum diet at ambient temperatures of 10, 15 and 25?°C. Torpor bout duration ranged from <1?h to ca. 18?h. The times of entry into torpor were restricted to the scotophase, despite normothermic body temperature patterns indicating a rest phase coincident with the photophase. Full arousal was always achieved within the first 3?h of the photophase. When food deprived, the onset of the rest phase, and hence torpor, advanced with respect to the experimental photoperiod. The lowest torpor body temperature measured was 9.41?°C. Daily torpor in M. proboscideus confirms a pleisiomorphic origin of daily heterothermy. Torpor facilitates risk-averse foraging behaviour in these small omnivores by overcoming long-term energy shortfalls generated by the inherent variability of food availability in their semi-arid, El Niño-afflicted habitats.     

Naloxone inhibition of stress-induced daily torpor

$\text{Peromyscus maniculatus}$, deermice, were induced into daily torpor by restricting food to one-half daily ration. Intraperitoneal injection of naloxone (20 mg/kg) into mice habituated to daily IP injections of saline inhibited or modified the expression of daily torpor. In those individuals demonstrating long duration/ deep bouts (greater than 300 min/body temperature 20°C or below) naloxone administration resulted in 1) a significant decrease in the duration of torpor, 2) a significant elevation in minimum body temperatures attained during torpor and 3) a significant delay in the initiation time of torpor. In those individuals demonstrating short duration/shallow bouts (less than 300 min/ body temperatures above 20°C), naloxone administration resulted only in a significant delay of initiation time. Upon subsequent return to saline administration, however, these mice displayed a significant increase in the duration and depth of torpor. The results suggest that the endogenous opiates modulate the state of daily torpor.     

Daily torpor alters multiple gene expression in the suprachiasmatic nucleus and pineal gland of the Djungarian hamster (Phodopus sungorus)

Circadian rhythms are still expressed in animals that display daily torpor, implying a temperature compensation of the pacemaker. Nevertheless, it remains unclear how the clock works in hypothermic states and whether torpor itself, as a temperature pulse, affects the circadian system. To reveal changes in the clockwork during torpor, we compared clock gene and neuropeptide expression by in situ hybridization in the suprachiasmatic nucleus (SCN) and pineal gland of normothermic and torpid Djungarian hamsters (Phodopus sungorus). Animals from light-dark (LD) 8ratio16 were sacrificed at 8 time points throughout 24 h. To investigate the effect of a previous torpor episode on the clock, we sacrificed a group of normothermic hamsters 1 day after torpor. In normothermic animals, Per1 peaked at zeitgeber time (ZT)4; whereas, Bmal1 reached maximal expression between ZT16 and ZT19. AVP mRNA in the SCN showed highest levels at ZT7. On the day of torpor, the levels of all mRNAs investigated, except for AVP mRNA, were increased during the torpor bout. Moreover, the Bmal1 rhythm was advanced. On the day after the hypothermia, Bmal1 and AVP rhythms showed severely depressed amplitude. Those distinct amplitude changes of Bmal1 and AVP on the day after a torpor episode expression suggests that torpor affects the circadian system, probably by altered translational processes that might lead to a modified protein feedback on gene expression. In the pineal gland, an important clock output, Aanat expression, peaked between ZT16 and ZT22 in normothermic animals. Aanat levels were significantly advanced on the day of hypothermia, an effect which was still visible 1 day afterward. In summary, this study showed that daily torpor affects the phase and amplitude of rhythmic clock gene and clock-controlled gene expression in the SCN. Furthermore, the rhythmic gene expression in a peripheral oscillator, the pineal gland, is also affected.     

Metabolism and temperature regulation during daily torpor in the smallest primate, the pygmy mouse lemur (Microcebus myoxinus) in Madagascar

Thermoregulation, energetics and patterns of torpor in the pygmy mouse lemur, Microcebus myoxinus, were investigated under natural conditions of photoperiod and temperature in the Kirindy/CFPF Forest in western Madagascar. M. myoxinus entered torpor spontaneously during the cool dry season. Torpor only occurred on a daily basis and torpor bout duration was on average 9.6 h, and ranged from 4.6 h to 19.2 h. Metabolic rates during torpor were reduced to about 86% of the normothermic value. Minimum body temperature during daily torpor was 6.8 °C at an ambient temperature of 6.3 °C. Entry into torpor occurred randomly between 2000 and 0620 hours, whereas arousals from torpor were clustered around 1300 hours within a narrow time window of less than 4 h. Arousal from torpor was a two-step process with a first passive climb of body temperature to a mean of 27 °C, carried by the daily increase of ambient temperature when oxygen consumption remained more or less constant, followed by a second active increase of oxygen consumption to further raise the body temperature to normothermic values. In conclusion, daily body temperature rhythms in M. myoxinus further reduce the energetic costs of daily torpor seen in other species: they extend to unusually low body temperatures and consequently low metabolic rates in torpor, and they employ passive warming to reduce the energetic costs of arousal. Thus, these energy-conserving adaptations may represent an important energetic aid to the pygmy mouse lemur and help to promote their individual fitness. Accepted: 2 November 1999     

Torpor patterns in the pouched mouse (Saccostomus campestris ; Rodentia): a model animal for unpredictable environments

Patterns of spontaneous and induced daily torpor were measured in the Afrotropical pouched mouse (77–115?g), Saccostomus campestris, in response to photoperiod, temperature, and food deprivation, using temperature telemetry. Photoperiod had no influence on the incidence, depth, or duration of daily torpor in either males and females. Although the testis size index decreased in response to food deprivation and photoperiod by a maximum of 24%, full testis regression did not occur. Torpor bout duration was, on average, 5.3?h, independent of photoperiod and ambient temperature. Males did not enter torpor in response to food deprivation but did in response to low ambient temperature, though significantly less frequently than females. At normothermia, the body temperatures (daily minimum, mean, maximum) of males were significantly lower than those of females. Minimum body temperatures of both males and females during torpor did not fall below 20?°C at an ambient temperature of 15?°C. The patterns of torpor measured here differ from those observed in species from strongly seasonal environments. They suggest adaptation to an environment rendered unpredictable by the El Niño Southern Oscillations. As an aseasonal, opportunistic breeder capable of year-round adaptive hypothermia, the pouched mouse represents an excellent model animal for research on physiological and behavioral adaptations to unpredictable environments.     

Torpor characteristics and energy requirements of furless Siberian hamsters.

After approximately 10 wk of exposure to decreasing day lengths, Siberian hamsters (Phodopus sungorus) begin to display spontaneous torpor bouts several times each week. Torpor is associated with reduced daily energy expenditure and lower food consumption and ameliorates the thermoregulatory challenges of winter. We tested the extent to which the energy savings conferred by daily torpor depend on the presence of an insulative pelage. Female hamsters were housed in a winter day length (8L:16D) at 5 degrees C; daily food intake and torpor characteristics were recorded for 5 wk in shaved (furless) or normal hamsters. Torpor-bout incidence decreased by 62% in furless hamsters, but the duration of individual bouts and the minimum body temperature attained during torpor were unaffected by loss of pelage. Body temperature declined more rapidly during entry into torpor and increased more slowly during arousal from torpor in furless than in control hamsters. Energy savings per torpor bout, assessed by the amount of food consumed on days that included a torpor bout, was substantially greater in normal than in furless hamsters (16.0% vs. 3.3%); this difference likely reflects the increased cost of thermoregulation during torpor, as well as the increased caloric expenditure incurred by furless hamsters during arousal from torpor. An insulative pelage may be a prerequisite for the energetic benefits derived from heterothermy in this species.     

Daily torpor in free-ranging rock elephant shrews, Elephantulus myurus: a year-long study

Under laboratory conditions, rock elephant shrews, Elephantulus myurus, use daily torpor under both short and long photoperiod acclimation. However, use of heterothermy often differs under field and laboratory conditions. We investigated the use of torpor in free-ranging elephant shrews from May 2001 to May 2002. The elephant shrews were capable of daily torpor throughout the year, with torpor most prevalent during winter. We recorded two torpor bouts during early summer (November). We recorded a total of 467 torpor bouts during the year. The mean torpor minimum body temperature (Tbmin) for the whole year was 15.3 degrees +/-4.4 degrees C, and the mean bout length was 8.6+/-3.5 h. These values were in the range expected for daily heterotherms. However, there was some marginal overlap with hibernation characteristics; a few torpor bouts were longer than 24 h in duration, and Tbmin decreased below 10 degrees C. Torpor was highly correlated with low ambient temperature and photoperiod. Torpor was also correlated with invertebrate abundance after controlling for photoperiod effects. During the year in which this study was conducted, the rainfall was 14% below long-term average. Historical rainfall records show that summer rainfall during strong El Nino years is up to 40% below the long-term average. During these drought years, the frequency of summer torpor may be higher, highlighting the need for long-term physiological data in free-ranging animals.     

Development of thermoregulation and torpor in a marsupial: energetic and evolutionary implications

Altricial mammals and birds become endothermic at about half the size of adults and presumably would benefit energetically from entering torpor at that time. Because little is known about torpor during development in endotherms, we investigated whether after the establishment of endothermic thermoregulation (i.e. the ability to maintain a high body temperature during cold exposure), Sminthopsis macroura, a small (∼25 g) insectivorous marsupial, is capable of entering torpor and whether torpor patterns change with growth. Endothermic thermoregulation was established when the nest young reached a body mass of ∼10 g, and they were capable of entering torpor early during development at ∼10–12 g, lending some support to the view that torpor is a phylogenetically old mammalian trait. Torpor bout length shortened significantly and the minimum metabolic rate during torpor increased as juveniles approached adult size, and consequently total daily energy expenditure increased steeply with age. Relationships between total daily energy expenditure and body mass during development of S. macroura (slope ∼1.3) differed substantially from the relationship between basal metabolism and body mass in adult endotherms (slope ∼0.75) suggesting that the energy expenditure–size relationship during the development differs substantially from that in adults under thermo-neutral conditions. Our study shows that while torpor can substantially reduce energy expenditure during development of endotherms and hence is likely important for survival during energy bottlenecks, it also may enhance somatic growth when food is limited. We therefore hypothesize that torpor during the development in endotherms is far more widespread than is currently appreciated.     

Melatonin production accompanies arousal from daily torpor in Siberian hamsters

Arousal from deep hibernation is accompanied by a transient rise of melatonin (Mel) in circulation; there are no comparable analyses of Mel concentrations in species that undergo much shallower, shorter duration episodes of daily torpor. Serum Mel concentrations were determined during arousal from both natural daily torpor and torpor induced by 2-deoxy-D-glucose (2-DG) treatment (2,500 mg/kg, intraperitoneal [IP]); blood samples were drawn from the retro-orbital sinus of anesthetized Siberian hamsters. For animals kept in darkness during torpor, Mel concentrations were highest during early arousal when thermogenesis is maximal, and they decreased as body temperature increased during arousal and returned to baseline once euthermia was reestablished. In hamsters kept in the light during the torpor bout, Mel concentrations were elevated above basal values during arousal, but the response was significantly blunted in comparison with values recorded in darkness. Increased Mel concentrations were detected in hamsters only during arousal from torpor (either natural or 2-DG induced) and were not simply a result of the drug treatment; hamsters that remained euthermic or manifested mild hypothermia after drug treatment maintained basal Mel concentrations. We propose that increased Mel production may reflect enhanced sympathetic activation associated with intense thermogenesis during arousal from torpor rather than an adjustment of the circadian rhythm of Mel secretion.     

Torpor and ultradian rhythms require an intact signalling of the sympathetic nervous system

During entrance into torpor heart and respiration rates are greatly reduced in parallel with the reduction of metabolic rate, suggesting an involvement of parasympathetic control. We compared the effect of parasympathetic inhibition with the effect of sympathetic inhibition on spontaneous torpor behaviour in the Djungarian hamster. Hamsters were acclimated to short photoperiod and displayed their standard torpor pattern as observed from T_b records. Parasympathetic inhibition was achieved by a subcutaneous implant of 21-day release pellets with Atropine and the sympathetic noradrenergic pathway was inhibited with a single injection of 6-Hydroxydopamine. Atropine treatment did not affect the occurrence and quality of spontaneous daily torpor at all. However, the reversible sympathetic inhibition by 6-Hydroxydopamine injection resulted in a complete disappearance of torpor for about 6 days. These results conclude that the onset of daily torpor requires an intact noradrenergic signalling of the sympathetic nervous system. We further observed that parasympathetic as well as sympathetic blockade resulted in an immediate abolishment of ultradian rhythms of body temperature. This suggests that the expression of ultradian oscillations in body temperature require a continued interaction of sympathetic and parasympathetic activity.     

Evidence of prolonged torpor in Goodman’s mouse lemurs at Ankafobe forest,central Madagascar

The small-bodied mouse lemurs of Madagascar (Microcebus) are capable of heterothermy (i.e., torpor or hibernation). The expression of these energy-saving strategies has been physiologically demonstrated in three species: M. berthae, the pygmy mouse lemur (daily torpor), M. murinus, the gray mouse lemur (daily torpor and hibernation), and M. griseorufus, the reddish-gray mouse lemur (daily, prolonged torpor and hibernation). Additional evidence, based on radiotracking and seasonal body mass changes, indicated that mouse lemur capabilities for heterothermy extended to M. lehilahytsara, the Goodman’s mouse lemur. In this study, we confirm the use of hibernation in Goodman’s mouse lemurs at a new location, a high-plateau forest fragment in Ankafobe, central Madagascar. Our evidence is based on sleeping site monitoring of radiocollared individuals and the retrieval of three mouse lemurs from inside a tree hole, all of which displayed a lethargic state. Though our data are preliminary and scant, we show that hibernation occurs in high-plateau mouse lemurs, and suggest that a buffered environment (i.e., tree holes instead of nests) may be crucial to avoiding potentially extreme ambient temperatures.     

Norepinephrine Controls Both Torpor Initiation and Emergence via Distinct Mechanisms in the Mouse

Some mammals, including laboratory mice, enter torpor in response to food deprivation, and leptin can attenuate these bouts of torpor. We previously showed that dopamine β-hydroxylase knockout (Dbh −/−) mice, which lack norepinephrine (NE), do not reduce circulating leptin upon fasting nor do they enter torpor. To test whether the onset of torpor in mice during a fast requires a NE-mediated reduction in circulating leptin, double mutant mice deficient in both leptin (ob/ob) and DBH (DBL MUT) were generated. Upon fasting, control and ob/ob mice entered torpor as assessed by telemetric core T_b acquisition. While fasting failed to induce torpor in Dbh −/− mice, leptin deficiency bypassed the requirement for NE, as DBL MUT mice readily entered torpor upon fasting. These data indicate that sympathetic activation of white fat and suppression of leptin is required for the onset of torpor in the mouse. Emergence from torpor was severely retarded in DBL MUT mice, revealing a novel, leptin-independent role for NE in torpor recovery. This phenotype was mimicked by administration of a β₃ adrenergic receptor antagonist to control mice during a torpor bout. Hence, NE signaling via β₃ adrenergic receptors presumably in brown fat is the first neurotransmitter-receptor system identified that is required for normal recovery from torpor.