Mechanisms underlying the supra-maximal thermogenesis elicited by aminophylline in rats

Previous studies showed that acute treatment with aminophylline (AMPY) significantly elevated maximum thermogenesis and improved cold tolerance in rats and man in severe cold. However, the exact mechanism by which AMPY enhances thermogenesis was unknown. Rats receiving enprofylline (ENPRO) (1.5 and 15 mg/kg, i.p.), a selective phosphodiesterase inhibitor, failed to show enhanced thermogenesis. In contrast, treatment with a selective adenosine receptor antagonist, 8-phenyltheophylline(8-PT; 2.5 to 10 mg/kg, i.p.), significantly increased (p less than 0.05) thermogenesis and cold tolerance. However, the maximal thermogenic effect by optimal dose of 8-PT (5 mg/kg) was significantly lower than that with optimal dose of AMPY (18.7 mg/kg, i.p.); the deficit could be eradicated by combining optimal 8-PT dose with a low dose of AMPY (1.25 mg/kg), but not with ENPRO. These results indicate that the thermogenic effect of AMPY is not by inhibition of phosphodiesterase but at least partially by antagonism of adenosine receptors. It is also apparent that older mechanisms in addition to adenosine antagonism are also involved in AMPY's thermogenic action.     

Effects of fasting and aminophylline on norepinephrine-stimulated non-shivering thermogenesis

In an attempt to further elucidate the mechanisms of fasting-depressed maximum thermogenesis and cold tolerance, norepinephrine (NE)-stimulated non-shivering thermogenesis (NST) in cold-acclimated rats was used as a functional index of possible alterations in adrenergic efficacy after fasting. Fasting decreased the magnitude of maximum NE-Stimulated NST by 18.2% [6.87±0.47 Kcal (Kg^.75.min)^?1 well-fed vs. 5.81±0.39 Kcal (Kg^.75.min)^?1 fasted], but the apparent adrenergic binding affinity was not affected [Ke=0.43 μg NE min^?1 well-fed vs 0.55 μg NE min^?1 fasted]. Pretreatment with aminophylline [15 mg Kg^?1, i.p.], a phosphodiesterase inhibitor, restored the fasting-depressed NE-stimulated NST to the fed level. The results suggest that the depression of maximum thermogenesis after fasting is not due to changes in adrenergic binding characteristics but to alteration in cAMP production/degradation, resulting in decreased substrate mobilization for thermogenesis.     

Substrate preference in aminophylline-stimulated thermogenesis

The present study investigated the suitability of different substrates on aminophylline (AMPY)-induced thermogenesis in rats during cold exposure. Feeding of distilled water 60 min prior to cold exposure in two-day fasted rats resulted in the lowest total heat production and final body temperature in both saline- and AMPY-treated groups. Feeding of 5 ml Intralipid (2 Kcal/ml), a triglyceride mixture, did not improve thermogenesis beyond the control levels. However, feeding of isocaloric substitutes of sucrose elevated significantly the total thermogenesis by 7.9% and 7.4% and final body temperature by 2.23 and 1.61 degrees C, respectively, in saline- and AMPY-treated groups. The increase in thermogenesis by sucrose is not due to its thermic effect. It is concluded that sucrose, in combination with AMPY, may be of value in improving resistance to cold.     

Cold adaptive thermogenesis in small mammals from different geographical zones of China

The mechanisms of thermogenesis and thermoregulation were studied in the tree shrew (Tupaia belangeri) and greater vole (Eothenomys miletus) of the subtropical region, and Brandt's vole (Microtus brandti), Mongolian gerbil (Meriones unguiculatus), Daurian ground squirrel (Spermophilus dauricus) and plateau pika (Ochotona curzoniae) of the northern temperate zone. Resting metabolic rate (RMR) and non-shivering thermogenesis (NST) increased significantly in T. belangeri, E. miletus, M. brandti and M. unguiculatus after cold acclimation (4 degrees C) for 4 weeks. In T. belangeri, the increase in RMR and thermogenesis at liver cellular level were responsible for enhancing the capacity of enduring cold stress, and homeothermia was simultaneously extended. Stable body temperature in M. brandti, E. miletus, M. unguiculatus and O. curzoniae was maintained mainly through increase in NST, brown adipose tissue (BAT) mass and its mitochondrial protein content, and the upregulation of uncoupling protein (UCP1) mRNA, as well as enhancement of the activity of cytochrome C oxidase, alpha-glycerophosphate oxidase and T(4) 5'-deiodinase in BAT mitochondria. The RMR in O. curzoniae and euthermic S. dauricus was not changed, while NST significantly increased during cold exposure; the former maintained their stable body temperature and mass, while body temperature in the latter declined by 4.8 degrees C. The serum T(3) concentration or ratio of T(3)/T(4) in all the species was enhanced after cold acclimation. Results indicated that: (1) the adaptive mechanisms of T. belangeri residing in the subtropical region to cold are primarily by increasing RMR and secondly by increasing NST, and the mechanisms of thermogenesis are similar to those in tropical mammals; (2) in small mammals residing in northern regions, the adaptation to cold is chiefly to increase NST; (3) the mechanism of cold-induced thermogenesis in E. miletus residing in subtropical and high mountain regions is similar to that in the north; (4) a low RMR in warm environments and peak RMR and NST in cold environments enabled M. unguiculatus to tolerate a semi-desert climate; (5) O. curzoniae has unusually high RMR and high NST, acting mainly via increasing NST to adapt to extreme cold of the Qinghai-Tibet Plateau; (6) the adaptation of euthermic S. dauricus to cold is due to an increase in NST and a relaxed homeothermia; and lastly (7) the thyroid hormone is involved in the regulation of cold adaptive thermogenesis in all the species studied.     

Supramaximal heat production induced by aminophylline in temperature-acclimated rats

Previous studies have shown that aminophylline, a phosphodiesterase inhibitor (thereby increasing intracellular cyclic AMP concentration) elicits supramaximal heat production and improves cold tolerance in rats acclimated to 22°C. To test whether aminophylline-stimulated supramaximal thermogenesis is independent of both the thermogenic capacity (i.e. aerobic fitness) and the mode of thermogenesis (shivering vs. non-shivering), rats (adult male Sprague-Dawley, approximately 400 g) of two different ages (4–11 month and 9–17 month, n=12 for each) were acclimated to 5, 15, and 25°C in succession and their thermogenic responses to aminophylline subsequently assessed. Aminophylline elicited supramaximal thermogenesis and improved cold tolerance regardless of age or acclimating temperatures. Further, the absolute net increase in heat production stimulated by aminophylline was also similar for all acclimating temperatures. After acclimating to 15°C, a single injection of aminophylline in the older rats elicited thermogenesis greater than that of the controls acclimated to 5°C; in the younger rats, aminophylline duplicated 46% of the increase in thermogenesis observed after acclimating to 5°C. These results indicated that the aminophylline-stimulated extra heat production is independent of both the thermogenic capacity and the mode of thermogenesis. It is possible that an enhanced substrate mobilization consequent to increased intracellular cyclic AMP concentration by aminophylline underlies the common mechanism via which supramaximal thermogenesis is elicited in temperature-acclimated rats.     

Effects of running training on in vitro brown adipose tissue thermogenesis in rats

Brown adipose tissue (BAT) is a major site of nonshivering thermogenesis (NST) during cold acclimation for most mammals. Repetitive nonthermal stress such as immobilization has been shown to enhance the capacity of NST as cold acclimation. In the present study, the effects of running training, another type of nonthermal stress, were investigated on in vitro thermogenesis and the cellularity of interscapular BAT in rats. The rats were subjected to treadmill running for 30 min daily at 30 m/min under 8° inclination for 4–5 weeks. In vitro thermogenesis was then measured in minced tissue blocks incubated in a Krebs-Ringer phosphate buffer containing glucose and albumin at 37° C, using a Clark type oxygen electrode. The trained rats showed less body weight gain during the experiment. The weights of BAT and epididymal white adipose tissue were smaller in the trained rats. Noradrenaline- and glucagon-stimulated oxygen consumption were also significantly smaller in the trained rats. The tissue DNA level was greater in the trained rats, but the DNA content per tissue pad did not significantly differ. The results indicate that running training reduces BAT thermogenesis, possibly as an adaptation to conserve energy substrates for physical work.     

Effects of cold exposure on cyclic AMP concentration in plasma,liver, and brown and white adipose tissues in cold-acclimated rats

Effects of acute cold exposure on plasma energy substrates and tissue 3,5-adenosine monophosphate (cAMP) were analyzed in intact rats, to define an involvement of the nucleotide in nonshivering thermogenesis (NST) and resultant cold acclimation. After an acute cold exposure to –5°C, the plasma glucose level increased gradually in warm-kept control rats (C) while it decreased significantly in cold-acclimated rats (CA). However, it was increased considerably by an extreme cold exposure to –15°C in both C and CA. By contrast, plasma levels of free fatty acids (FFA) increased immediately after cold exposure and the release lasted during the period of exposure especially in C. The cold exposure also increased plasma cAMP concentration but no concomitant increase was found in the liver. In both brown (IBAT) and white (WAT) adipose tissues the nucleotide concentration showed a stepwise decrease. The observed correlation between lipolysis and plasma cAMP response after cold exposure suggests an involvement of the adenylate cyclase-cAMP system in NST via lipid metabolism, at least, in the early stages of cold acclimation.Abbreviations cAMP cyclic 3,5-adenosine monophosphate - NST nonshivering thermogenesis - FFA free fatty acids - IBAT brown adipose tissue - WAT white adipose tissue     

Effect of food restriction on cold adaptability of rats

To determine the role of the nutritional state in nonshivering thermogenesis during cold adaptation, cold adaptability was compared between cold-adapted (5 degrees C for 4-5 weeks) rats fed ad libitum and cold-adapted rats pair fed with warm controls having the same food intake. Cold-adapted pair-fed rats suffered a significant loss in body weight during cold exposure. However, brown adipose tissue (BAT) in both cold-adapted ad libitum fed and cold-adapted pair-fed rats was enlarged to the same extent as compared with that in control rats. Fat-free dry matter in BAT also increased in cold-adapted ad libitum fed and cold-adapted pair-fed rats to the same extent. Cold tolerance as assessed by the change in the colonic temperature at -5 degrees C was improved relative to control rats and was the same for cold-adapted ad libitum fed and cold-adapted pair-fed rats. Nonshivering thermogenesis as estimated by the noradrenaline-induced increase in oxygen consumption was significantly greater in the cold-exposed rats and there was no significant difference between cold-adapted ad libitum fed and cold-adapted pair-fed rats. These results suggest that an improved cold tolerance by means of nonshivering thermogenesis in brown adipose tissue is closely related to the low temperature itself but not the increased food intake which occurred in the cold.     

Seasonal adjustments in body mass and thermogenesis in Mongolian gerbils (<Emphasis Type="Italic">Meriones unguiculatus</Emphasis>): the roles of short photoperiod and cold

Seasonal adjustments in body mass and thermogenesis are important for the survival of small mammals during acclimatization in the temperate zone. To determine the contributions of short photoperiod and cold temperatures to seasonal changes in thermogenesis and body mass in Mongolian gerbils (Meriones unguiculatus), body mass, basal metabolic rate (BMR), nonshivering thermogenesis (NST), energy intake and energy digestibility were determined in seasonally acclimatized and laboratory acclimated animals. Body mass showed significant seasonal changes and decreased to a minimum in winter. Both BMR and NST increased in winter, and these changes were mimicked by exposing animals to short photoperiod or cold temperatures in the animal house. Digestible energy intake also increased significantly in winter, and also during exposure of housed animals to both short photoperiod and cold. These results suggest that Mongolian gerbils overcome winter thermoregulatory challenges by increasing energy intake and thermogenesis, and decreasing body mass to reduce total energy requirements. Short photoperiod and cold can serve as effective environmental cues during seasonal acclimatization.     

When nonshivering thermogenesis equals maximum metabolic rate: thermal acclimation and phenotypic plasticity of fossorial Spalacopus cyanus (Rodentia)

Many small mammals inhabiting fluctuating and cold environments display enhanced capacity for seasonal changes in nonshivering thermogenesis (NST) and thermoregulatory maximum metabolic rate (MMR). However, it is not known how this plasticity remains in a mammal that rarely experiences extreme thermal fluctuations. In order to answer this question, we determined body mass (m(b)), basal metabolic rate (BMR), NST, MMR, and minimum thermal conductance (C) on a Chilean fossorial caviomorph (Spalacopus cyanus) from a coastal population, acclimated to cold (15 degrees C) and warm (30 degrees C) conditions. NST was measured as the maximum response of metabolic rate (NST(max)) after injection of norepinephrine (NE) in thermoneutrality minus BMR. Maximum metabolic rate was assessed in animals exposed to enhanced heat-loss atmosphere (He-O2) connected with an open-flow respirometer. Body mass and metabolic variables increased significantly after cold acclimation with respect to warm acclimation but to a low extent (BMR, 26%; NST, 10%; and MMR, 12%). However, aerobic scope (MMR/BMR), calculated shivering thermogenesis (ST), and C did not change with acclimation regime. Our data suggest that physiological plasticity of S. cyanus is relatively low, which is in accordance with a fossorial mode of life. Although little is known about MMR and NST in fossorial mammals, S. cyanus has remarkably high NST; low MMR; and surprisingly, a nil capacity of ST when compared with other rodents.     

The effects of reduced temperature and photoperiod on body composition in hibernator and non-hibernator rodents

We examined the differential change in body composition in response to a gradual reduction in both environmental temperature and photoperiod to mimic seasonal fluctuations in the wild (summer–winter transition), from ambient to 5°C and 1:23 light:dark for 8 weeks. In contrast to acute cold exposure used in previous studies, cold-acclimated rats showed an initial increase in growth rate relative to normothermic controls, possibly due to cold-stimulated hyperphagia. In hamsters, maintenance of growth rate during initial cold exposure reflects the intrinsic high oxidative capacity, while subsequent cessation of growth is consistent with the preparation for hibernation. Cold-induced atrophy of skeletal muscles coincided with increased capacity for non-shivering thermogenesis (NST) associated with a greater mass of brown adipose tissue (BAT). Cardiac hypertrophy may compensate for an increase in total peripheral resistance and/or work load of heart in both species (40% and 20%, respectively), while hypertrophy of lung (20% and 40%) and diaphragm muscle (7% and 40%) was consistent with increased ventilation associated with a cold-induced increase in basal metabolic rate. Gonadal atrophy in hamsters (160%) may be an energy saving strategy during the non-reproductive season, while maintenance of other endocrine (thyroid, adrenal, pineal) gland masses reflects the continued importance of hormonal regulation of homeostasis. The interspecific differences appear to accommodate the increased demands of shivering thermogenesis (skeletal muscle hypertrophy) or NST (BAT, diaphragm) in rats and hamsters, respectively. Those systems representing cardiovascular and metabolic control completed their adaptation quickly (within 4-week cold acclimation), while the respiratory and reproductive systems continued to respond to a further 4-week exposure. This differential time course may reflect the relative strength of selection pressure on these systems for the process of cold acclimation.     

Contribution of shivering and nonshivering thermogenesis to thermogenic capacity for the deer mouse (Peromyscus maniculatus)

Small mammals that are active all year must develop ways to survive the cold winters. Endotherms that experience prolonged cold exposure often increase their thermogenic capacity. Thermogenic capacity incorporates basal metabolic rate (BMR), nonshivering thermogenesis (NST), and shivering thermogenesis (ST). Increasing the capacity of any of these components will result in increased thermogenic capacity. It is often thought that NST should be the most plastic component of thermogenic capacity and as such is the most likely to increase with cold acclimation. We used deer mice to test this hypothesis by acclimating 27 animals to one of two temperatures (5 degrees or 22 degrees C) for 8 wk. We then measured and compared values for thermogenic capacity--BMR, ST, and NST--between the two groups. Thermogenic capacity and NST increased by 21% and 42%, respectively, after cold acclimation. Neither BMR nor ST showed any change after acclimation. Therefore, it appears that deer mice raise their thermogenic capacity in response to prolonged cold by altering NST only.     

Changes in plasma cortisol during acute cold exposure in euthermic European hedgehogs: thermoregulatory role of the hypothalamo-pituitary-adrenal axis

Summary During acute cold exposure regulatory heat production of European hedgehogs was significantly increased with a simultaneous rise in the plasma cortisol level. Soon after cold exposure, at the time when standard metabolic rate was measured, the plasma cortisol level was reduced again. This finding indicates a highly reactive hypothalamo-pituitary-adrenal axis in euthermic hedgehogs exposed to a cold environment.Two effects of the adrenocorticostatic agent metopirone ditartrate were observed: (1) A metopirone-induced increase in nonshivering thermogenesis (NST) starting 18 min after application, reaching a maximum after 43 min and disappearing after 90 min (Fig. 1, Table 1). Simultaneously a profound long lasting hyperglycemia was observed (Fig. 2). (2) In contrast to untreated hedgehogs, animals which were given metopirone did not show an increase in the plasma cortisol level, when exposed to cold within 2 to 3 h (Fig. 6).When animals were pretreated with dexamethasone the metopirone-induced NST was suppressed, indicating that the effect of metopirone is mediated by the hypothalamo-pituitary-adrenal system (Fig. 4).The effect of metopirone at doses used in this study was reversible.It is suggested that a combined action of corticosteroids and catecholamines is involved in the control of regulatory heat production.Abbreviations SMR standard metabolic rate - NST nonshivering thermogenesis Supported by the Deutsche Forschungsgemeinschaft Wu 63/5     

Alterations in thyroid hormone physiology induced by temperature and feeding in newly hatched chickens

In the chicken the transition of a poikilotherm to a homeotherm reaction upon cold exposure takes place in the perinatal period between pipping and hatching. However, newly hatched chicks cannot maintain their body temperature within narrow limits after cold exposure. The fact that relatively little attention was payed on the role of thyroid hormones in the thermoregulatory reaction to cold of young chicks was probably due to the hypothetically long latention time that was thought to be necessary to bring about changes in secretory activity by cold stimulation. However, more recently, rapid changes (within hours) of thyroid hormone concentrations upon cold exposure were described in the chickens and the quail. In this study, changes in circulating T3 and T4 concentrations upon cold exposure of young chicks during the first two weeks were followed, that means during the period wherein NST (non-shivering thermogenesis), if it exists at all, should be progressively replaced by ST (shivering thermogenesis). Because of the importance of feeding condition on thyroid hormone levels, the experiments were carried out with and without a preceeding fasting period. In all experiments a short-term cold exposure of young chickens (1-11 days) fed ad lib decreased T3 but increased T4 levels while a reversed picture was found after short cold exposure of the fasted animals. However, after prolonged cold stimulus (15 degrees C) of young chickens fed ad lib, plasma T3 was also significantly elevated over that of controls whereas T4 levels returned to normal values. A prolonged warm treatment (37 degrees C) of young chickens fed ad lib resulted in significantly lower T3 and higher T4 concentrations. After a prolonged cold treatment no differences in T4 or T3 response upon TRH were found whereas the warm treatment abolished these responses upon TRH. However, a cold treatment at the stage of incubation during which the hypothalamo-hypophyseal control of thyroid function is established (dag 10-14) enhanced the T4 response to TRH with a long lasting effect extending to the posthatch period. Since T3 is thought to be the active form of thyroid hormones with regard to thermopoiesis we have studied more specifically the effect of blocking peripheral conversion of T4 on thermoregulatory abilities in young chicks and the influence of temperature treatment on monodeiodination capacity. The lower rectal temperatures following the interference with the peripheral monodeiodination of T4, the effect being more pronounced at the lower ambient temperature, are indicative for a preponderant role of T3 on thermogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Seasonal changes in body mass and thermogenesis in tree shrews (Tupaia belangeri): The roles of photoperiod and cold

Environmental factors play an important role in the seasonal adaptation of body mass and thermogenesis in small, wild mammals. To determine the contributions of photoperiod and cold on seasonal changes in energy metabolism and body mass, the resting metabolic rates (RMR), nonshivering thermogenesis (NST), energy intake and gut morphology of the tree shrews were determined in winter and summer and in laboratory acclimated animals. Body mass, RMR and NST increased in winter, and these changes were mimicked by exposing animals to short-day photoperiod or cold in the animal house. Energy intake and digested energy also increased significantly in winter, and also during exposure of housed animals to both short-day photoperiod and cold. The lengths and weights of small intestine increased in winter. These results indicated that Tupaia belangeri overcomes winter thermoregulatory challenges by increasing energy intake and thermogenesis, and adjusted gut morphology to balance the total energy requirements. Short-day photoperiod and cold can serve as environmental cues during seasonal acclimatization.     

Brown fat and nonshivering thermogenesis in the gray mouse lemur (Microcebus murinus)

The gray mouse lemur Microcebus murinus is a rare example of a primate exhibiting daily torpor. In captive animals, we examined the metabolic rate during arousal from torpor and showed that this process involved nonshivering thermogenesis (NST). Under thermoneutrality (28 degrees C), warming-up from daily torpor (body temperature <33 degrees C) involved a rapid (<5 min) increase of O(2) consumption that was proportional to the depth of torpor (n = 8). The injection of a beta-adrenergic agonist (isoproterenol) known to elicit NST induced a dose-dependent increase in metabolic rate (n = 8). Moreover, maximum thermogenesis was increased by cold exposure. For the first time in this species, anatomic and histological examination using an antibody against uncoupling protein (UCP) specifically demonstrated the presence of brown fat. With the use of Western blotting with the same antibody, we showed a likely increase in UCP expression after cold exposure, suggesting that NST is also used to survive low ambient temperatures in this tropical species.     

Oxidative phosphorylation by in situ synaptosomal mitochondria from whole brain of young and old rats

Synaptosomes, isolated from the whole brain of young (3 months) and old (24 months) rats were used to study the major bioenergetic systems of neuronal mitochondria in situ, within the synaptosome. Approximately 85% of the resting oxygen consumption of synaptosomes from both young and old rats was a result of proton leak (and possibly other ion cycling) across the mitochondrial inner membrane. There were no significant differences between synaptosomes from the young and old rats in the kinetic responses of the substrate oxidation system, the mitochondrial proton leak and the phosphorylation system to changes in the proton electrochemical gradient. Flux control coefficients of 0.71, 0.27 and 0.02 were calculated for substrate oxidation system, phosphorylation system and the proton leak, respectively, at maximal ATP producing capacity in synaptosomes from young animals. The corresponding values calculated for synaptosomes from old animals were 0.53, 0.43 and 0.05. Thus substrate oxidation had greatest control over oxygen consumption at maximal phosphorylating capacity for synaptosomes from whole brain, with proton leak, having little control under maximal ATP producing capacity. The uncoupled rate of oxygen consumption, in the presence of the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), was significantly lower (p = 0.0124) in synaptosomes from old rats (6.08 +/- 0.42, n = 11) when compared with those from the young rats (7.87 +/- 0.48, n = 8). Thus, there is an impaired flux through the substrate oxidation system is synaptosomes from old rats, as compared to synaptosomes from the young animals. These in situ results may have important implications for the interpretation of theories that age-dependent impairment of mitochondrial energy production may result in increased susceptibility to neurodegeneration.     

Intensity of gluconeogenesis in liver tissue of rats of various age groups]

Intensity of glucose synthesis from different substrates in the liver slices was investigated in 1-, 13-15-, 30-day old and adult (3-6 month old) rats. Maximal gluconeogenesis activity was observed in the liver tissue of 13-15 day old rats. There was a change in the substrate specificity of gluconeogenesis during ontogenesis. Under cold stress and low body temperature (30 degrees C) a rate of gluconeogenesis from some substrates in young rats increased, while in adults-decreased. The activation of gluconeogenesis in adult rats occurred only at prolonged hypothermia to 3 h and almost complete exhaustion of glycogen reserves in the liver.     

Exercise suppression of thermoregulatory thermogenesis in warm- and cold-acclimated rats

An evaluation was made of the effects of an acute exercise bout on nonshivering thermogenesis (NST) in cold-acclimated rats (4 degrees C for 6 weeks) and shivering thermogenesis in 24 degrees C-acclimated rats (24 degrees C for 6 weeks). Assessment techniques included indirect calorimetry during treadmill running and brown adipose tissue (BAT) mitochondrial guanosine diphosphate (GDP) binding immediately following a treadmill run. Calorimetric results for 24 degrees C-acclimated rats running at 4 degrees C indicated total substitution of shivering thermogenesis by exercise-derived heat. No difference in GDP-binding, an index of BAT nonshivering thermogenic activity, was observed between exercised and nonexercised 24 degrees C-acclimated rats. Calorimetric results for cold-acclimated rats running at 4 degrees C indicated a total suppression in the energy cost associated with NST, exercise-derived heat replacing or substituting for NST. Examining BAT properties in the exercised cold-acclimated rats revealed a significant 40% decrease in BAT mitochondrial GDP-binding. These results suggest that during running, metabolic heat due to the exercise totally replaces shivering in 24 degrees C-acclimated rats and totally replaces BAT nonshivering thermogenesis in cold-acclimated rats.     

Nonshivering thermogenesis in a marsupial (the tasmanian bettong Bettongia gaimardi) is not attributable to brown adipose tissue

The Tasmanian bettong (Bettongia gaimardi, a marsupial) is a rat-kangaroo that increases nonshivering thermogenesis (NST) in response to norepinephrine (NE). This study attempted to assess whether brown adipose tissue (BAT), a specialized thermogenic effector, is involved in NST in the bettong. Regulatory NST, indicated by resting oxygen consumption (Vo2) of the whole body, was measured under conscious conditions at 20 degrees C with various stimuli: cold (4 degrees -5 degrees C) or warm (25 degrees C) acclimation, NE injection, and the beta3-adrenoceptor agonist (BRL) 37344. In line with the functional studies in vivo, the presence of BAT was evaluated by examining the expression of the uncoupling protein 1 (UCP1) with both rat cDNA and oligonucleotide probes. Both NE and BRL 37344 significantly stimulated NST in the bettong. After cold acclimation of the animals (at 4 degrees -5 degrees C for 2 wk), the resting Vo2 was increased by 15% and the thermogenic effect of NE was enhanced; warm-acclimated animals showed a slightly depressed response. However, no expression of UCP1 was detected in bettongs either before or after cold exposure (2 wk). These data suggest that the observed NST in the marsupial bettong is not attributable to BAT.