Regulatory Nonshivering Thermogenesis Research Articles

Brown adipose tissue plays thermoregulatory role within the thermoneutral zone in Mongolian gerbils (Meriones unguiculatus)

Brown adipose tissue (BAT) plays an important role in thermoregulation and many metabolic processes in small mammals, especially in cold adaptation. However, in warm adaptation, ambient temperature cannot directly activate BAT by sympathetic nervous system. Mongolian gerbils exhibit a wider thermoneutral zone (26.5-38.9 °C). We hypothesized that BAT atrophied near the lower critical temperature and further atrophied near the upper critical temperature. Male gerbils were acclimated to 23 °C, 27 °C or 37 °C, respectively, for 3 weeks. Results showed that regulatory non-shivering thermogenesis did not change in gerbils acclimated to 27 °C compared with 23 °C group, whereas it was reduced by 43.5% in gerbils acclimated to 37 °C. Bigger lipid droplet in BAT was observed in gerbils acclimated to 27 °C and 37 °C compared with 23 °C group, while the expression of uncoupling protein 1 and tyrosine hydroxylase was only reduced in gerbils acclimated to 37 °C. Further, thermoneutral acclimation did not change BAT thermogenesis by down-regulation of peroxisome proliferator-activated receptor gamma coactivator-1α, PR domain containing 16, peroxisome proliferator-activated receptor-α or peroxisome proliferator activated receptor-γ gene expression in BAT. In addition, body temperature was reduced in gerbils acclimated to 37 °C compared with 23 °C group, which was associated with a decreased resting metabolic rate and regulatory non-shivering thermogenesis. In conclusion, BAT does not atrophy near the lower critical temperature, whereas it atrophies near the upper critical temperature, suggesting that BAT may play thermoregulatory role within the TNZ in Mongolian gerbils.

Seasonal and Sexual Variation in Metabolism, Thermoregulation, and Hormones in the Big Brown Bat (Eptesicus fuscus)

In response to seasonal variation in energy availability and thermal environment, physiological and endocrine mechanisms have evolved in temperate zone animals. Seasonal changes in hormone activity affect metabolism, body temperature, and reproductive activity. We examined the seasonal regulatory role of hormones on basal metabolic rate (BMR) and regulatory nonshivering thermogenesis (RNST) in 98 female and 17 male adult Eptesicus fuscus (big brown bat). We measured BMR, RNST, and plasma levels of thyroid hormone (T3), leptin, and cortisol in bats captured in maternity colonies in eastern Massachusetts from May to August (from arousal from the hibernation phase to the prehibernation phase). We hypothesized that all three hormones are seasonally primarily metabolic hormones and secondarily thermogenic hormones. In males, only BMR significantly changed seasonally. In females, all five variables significantly changed seasonally. The seasonal pattern of plasma leptin and cortisol levels correlated with the seasonal pattern of BMR, with an initial increase followed by a decrease, suggesting that leptin and cortisol are primarily metabolic hormones. The seasonal pattern of plasma T3 levels generally paralleled the basic seasonal pattern of RNST, with both increasing at the second half of the season, suggesting that T3 is primarily a thermogenic hormone. The observed decrease in plasma leptin levels may be necessary to allow for the observed seasonal decrease in BMR, with the similar cortisol pattern important for leptin regulation. While T3 is needed to maintain BMR, it may play a more critical role in the seasonal regulation of RNST than of BMR.

Cold-acclimation-induced non-shivering thermogenesis in birds is associated with upregulation of avian UCP but not with innate uncoupling or altered ATP efficiency

Despite their lack of brown adipose tissue, some bird species develop regulatory non-shivering thermogenesis (NST) of skeletal muscle origin in response to cold acclimation. Mechanisms involved in avian NST are still unclear but may involve reduced energetic coupling in skeletal muscle mitochondria through the expression of an avian homologue of mammalian uncoupling proteins. The aim of this work was to investigate whether the expression of avian uncoupling protein (avUCP) would correlate with the capacity for cold-induced muscle NST. Various levels of cold acclimation were obtained by rearing 1-week-old ducklings (Cairina moschata) for 4 weeks at three different ambient temperatures (25 degrees C, 11 degrees C or 4 degrees C). Muscle NST was measured by simultaneous recordings of metabolic rate and electromyographic activity (gastrocnemius muscle) at ambient temperatures (T(a)) ranging from 27 degrees C to -5 degrees C. The expression of avUCP gene and mitochondrial bioenergetics were also determined in gastrocnemius muscle. Results showed that muscle NST capacity depends on the T(a) at which ducklings were acclimated, i.e. the lower the rearing temperature, the higher the capacity for NST. This increased metabolic heat production occurred in parallel with an upregulation of avUCP, which was not associated with a change in mitochondrial membrane conductance. The intensity of mitochondrial oxidative phosphorylation also increased in proportion with the harshness of cold, while the efficiency of ATP generation was equally effective in all three acclimation temperatures. In the absence of mitochondrial uncoupling, these data indicate a clear link between avUCP expression and the capacity of ducklings to adjust their muscular aerobic activity to cold exposure.

Nonshivering thermogenesis capacity versus basal metabolic rate in laboratory mice

I wanted to follow the correlation between level of basal metabolic rate (BMR) and maximum response to injection of noradrenaline (MMR NA) in two lines of laboratory mice subjected to divergent, artificial selection toward high BMR (HBMR) and low BMR (LBMR). HBMR animals had heavier visceral organs (heart, liver, kidney, intestine), but their regulatory NST (MMR NA–BMR) was lower and interscapular brown adipose tissue (IBAT) lighter than in LBMR mice. Obligatory part of nonshivering thermogenesis (NST) (in other words BMR) depended on visceral organ mass, whereas regulatory NST correlates with mass of IBAT. BMR was not correlated with total NST capacity, but phenotypic correlation between obligatory and regulatory NST was negative. This suggests possibility of substitution of obligatory NST to thermoregulation in a place of the regulatory NST. Then total thermoregulatory energy expenditures do not change.

Mole-rats from higher altitudes have greater thermoregulatory capabilities

Subterranean mammals (those that live and forage underground) inhabit a challenging microenvironment, with high levels of carbon dioxide and low levels of oxygen. Consequently, they have evolved specialised morphological and physiological adaptations. For small mammals that inhabit high altitudes, the effects of cold are compounded by low oxygen partial pressures. Hence, subterranean mammals living at high altitudes are faced with a uniquely demanding physiological environment, which presumably necessitates additional physiological adjustments. We examined the thermoregulatory capabilities of two populations of Lesotho mole-rat Cryptomys hottentotus mahali that inhabit a ‘low’ (1600 m) and a ‘high’ (3200 m) altitude. Mole-rats from the high altitude had a lower temperature of the lower critical point, a broader thermoneutral zone, a lower thermal conductance and greater regulatory non-shivering thermogenesis than animals from the lower altitude. However, minimum resting metabolic rate values were not significantly different between the populations and were low compared with allometric predictions. We suggest that thermoregulatory costs may in part be met by animals maintaining a low resting metabolic rate. High-altitude animals may adjust to their cooler, more oxygen-deficient environment by having an increased non-shivering thermogenesis whilst maintaining low thermal conductance.

Daily rhythms of nonshivering thermogenesis and responses to photoperiod manipulations in Apodemus mystacinus from two different ecosystems

Comparative physiology is an important tool for understanding adaptation to environment. Regulatory nonshivering thermogenesis (NST) is an essential mechanism in small mammals for coping with low ambient temperatures. Because of its geographical location and its sharp climatic changes across short distances, Israel offers conducting comparative studies between different populations of the same species. The aims of this study were: (1) to compare NST-capacity daily rhythms, between the two populations of the broad-toothed field mouse Apodemus Mystacinus—that of Mount Carmel (Mediterranean) and that of Mount Hermon (Subalpinic), (2) to compare the thermoregulatory daily rhythms response to photoperiod manipulations of mice from the two populations. Mice were acclimated for at least 3 weeks to long scotophase (16D:8L-LS) and then to long photophase (16L:8D-LP) at a constant ambient temperature ( T a) of 24±1 °C. The following variables were compared at four different times of the day (06, 12, 18, 24 h): minimal body temperature ( T bMin), minimal oxygen consumption (VO 2Min) measured at the lower critical point and their response to noradrenaline (NA), 1.5 mg/1 kg. W b injected s.c., (VO 2NA and T bNA). NST-capacity was calculated as the ratio between VO 2NA and VO 2Min. The measurements were carried out at T a of 28 °C and in light conditions matching those of acclimation. NA was injected after establishing VO 2Min and T bMin. The values mean±SD are given for each measurement for n = 6 . A three-way ANOVA revealed a significant difference between the two populations. Significant differences were revealed at different hours within populations under the different photoperiod regimes for different measured variables.

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.

Summer acclimatization in the short-tailed field vole, Microtus agrestis.

We investigated the changes that occurred in basal and noradrenaline-induced metabolic rate, body temperature and body mass in short-tailed field voles, Microtus agrestis, during exposure to naturally increasing photoperiod and ambient temperature. These parameters were first measured in winter-acclimatized voles (n = 8) and then in the same voles which had been allowed to seasonally acclimatize to photoperiod and ambient temperature (6 months later). Noradrenaline induced metabolic rate, basal metabolic rate and non-shivering thermogenesis were significantly higher in winter-acclimatized compared to summer-acclimatized voles. There was a significant positive relationship between basal metabolic rate and noradrenaline-induced metabolic rate. Body mass was significantly higher in summer-acclimatized compared to winter-acclimatized voles. There was a significant positive relationship between body mass and noradrenaline-induced metabolic rate in both winter-acclimatized and summer-acclimatized voles; however, there was no relationship between basal metabolic rate and body mass in either seasonal group of voles. Body temperature after measurements of basal metabolic rate was not significantly different in the seasonal cohorts of voles. However, body temperature was significantly higher in winter-acclimatized compared to summer-acclimatized voles after injection of noradrenaline. Previously we have found that a long photoperiod was not a sufficient stimulus to reduce thermogenic capacity in winter-acclimatized voles during cold exposure, since basal metabolic rate increased to compensate for a reduction in regulatory non-shivering thermogenesis. Here we found that a combination of increased ambient temperature and photoperiod did significantly reduce thermogenic capacity in winter-acclimatized voles. This provided evidence that the two aspects of non-shivering thermogenesis, obligatory and regulatory, are stimulated by different exogenous cues. Summer acclimatization in the short-tailed field vole is manifest as a significant decrease in both basal and noradrenaline-induced metabolic rate, combined with a significant increase in body mass.

Energetics and Development of Temperature Regulation in Capercaillie Tetrao urogallus

Thermoregulatory capacities of newly hatched and developing capercaillie chicks (Tetrao urogallus) were studied. Metabolic rate and body temperature measurements were conducted at ambient temperatures ($T_{a}$) between -30 and 37 C. The chicks rely primarily on behavioral thermoregulation. A sudden increase of basal heat production at the age of 4-5 days constitutes an important element in the control of stable body temperature ($T_{b}$) and coincides with the gradual elevation of the body temperature and capacity to stimulate thermoregulatory heat production. Chicks 1-3 days old can more than double their metabolic rate at 15 C. There is no evidence of regulatory nonshivering thermogenesis. Consequently, the only way to increase heat production is to stimulate muscular activity either by shivering or by voluntary muscular activity. The most rapid development of thermoregulatory capacity occurs at the age of 7-11 days, which may be correlated with the synergistic maturation of neuronal thermoregulatory co...

Metabolic organization of muscle and brown fat of normal and dystrophic hamsters

The thermogenic response to catecholamines, i.e., regulatory nonshivering thermogenesis (NST), is significantly reduced in dystrophic hamsters (BIO 14.6) compared with age-matched normals. The possibility that this reduction reflects, in part, lower levels of enzymes in those tissues implicated in NST has been examined by assaying citrate synthase (CS), beta-hydroxyacyl CoA dehydrogenase (HOAD), and phosphofructokinase (PFK), enzymes whose activity reflect the potential flux of substrates through the tricarboxylic acid cycle, beta-oxidation, and glycolysis, respectively. Each enzyme was assayed in brown fat, heart, gastrocnemius, and semitendinosus of 3-mo-old normal (n = 15) and dystrophic (n = 18) hamsters. Brown fat masses from interscapular, cervical, and scapular-axillary regions of dystrophics averaged only 50% those of normals (424 vs. 890 mg). Additionally, markers of aerobic metabolism (CS and HOAD) were significantly reduced in the brown fat from dystrophic animals. (CS activities averaged 59% of normal, whereas HOAD activities averaged 75% of normal). In dystrophic animals CS and HOAD levels were similar to those of normals in cardiac tissue but were significantly elevated in skeletal muscle samples. Tissue PFK activities were reduced only in cardiac tissue of the more affected dystrophics. Thus decreased NST capacity in dystrophic hamsters is accompanied by reduced masses and CS values in brown fat but not by decreases in the aerobic markers in skeletal or cardiac muscle.

Thermoregulatory heat production in cold-reared and warm-reared pigs.

Pigs were reared from 2 wk of age in either 10 or 35 degrees C and fed ad libitum. At 8 wk of age they were tested for the presence of regulatory nonshivering thermogenesis by administration of norepinephrine (NE) and propranolol. In addition, an electromyogram and carotid temperature, as well as a heat flow and skin temperature from one site, were monitored while the pigs were at ambient temperatures of 10, 15, 20, 25, and 30 degrees C. Cold-reared pigs showed a heightened response to NE in cold compared to thermally neutral environments. This was not observed in warm-reared pigs. Propranolol depressed O2 consumption more in cold-reared than in warm-reared pigs. Pigs reared in the cold also showed a higher intensity of shivering, tissue conductance, and skin temperature than warm-reared littermates. The shivering response of cold-reared pigs was more sensitive to changes in skin temperature than in warm-reared pigs.

Prediction of Obligatory and Regulatory Non-shivering Thermogenesis and Shivering Thermogenesis in Man

Physiological thermogenesis in intemal organs as well as main muscle groups is one of the most important subjects in the study of human adaptability to cold environment. The experiments of the prediction of obligatory non-shivering thermogenesis were performed under optimal thermal condition in summer and in winter by using a prediction method of local muscle energy metabolic rate and quasi-basal metabolic rate B1 (Yokayama, 1980). B1 means the sum of metabolic rates other than those of main muscle groups. The subjects were eleven Japanese males in sumrner and ten Japanese males in winter. Subject YS was longitudinally examined to confirm seasonal change of obligatory non-shivering thermogenesis. Subject YS was performed to examine regulatory non-shivering thermogenesis and shivering thermogene-sis by using nine resting and static exercising items of back cold and front cold under three cold environments (T=-l0°C, -5°C and 0°C. In the summer experiments Bls were 32.43 (mean) ±12.59 (S.D.) kcal/h and B1/A= 19.81 ±9.26 kcal/m2 h. On the other hand, the results of the winter experiments were 67.32±7.83 kcal/h and B1/A=38.90±5.27 kcal/m3h. This tendency of the seasonal variation that the quasi-basal metabolic rate B1 in winter was greater than in summer was coincident with the results in winter and in summer obtained from the same subject YS. In subject YS the predicted B1S were 29.87 in summer, 57.84 in December and 55.55 and 57.92 kcal/h in March. In order to evaluate regulatory non-shivering thermogenesis, the predictions of B1 were performed from item-e of back cold and front cold under cold environments. B1 under T=-5°C and T=0°C were 78.19 and 83.13 kcal/h respectively. Therefore the value of regulatory non-shivering thermogenesis was about 22 kcal/h under the present experimental conditions. The shivering thermogenesis was predicted for six to nine muscle groups in nine resting and exercising items of back cold and front cold under three cold environments

Total body and splanchnic thermogenesis in curarized man during a short exposure to cold.

To investigate thermoregulation independent of muscular contractions in adult man during a short period of exposure to cold, five examinations were carried out on four individuals who were unconscious due to persistent brain damage and who were totally curarized during the exposure. An increase was found in total body oxygen consumption of 0.043 mmol . kg-1 (range 0.038-0.049) or 25%, in plasma noradrenaline of 5.05 nmol . 1-1 (range: 2.48-6.73) or 132%, and in plasma non-esterified fatty acids of 0.6 mmol . -1 (range: 0.049-0.095) or 44%. No changes occurred in plasma adrenaline or plasma glucose. Splanchnic oxygen consumption increased and contributed significantly to that of the total body in only one of the four cases. These results indicate that regulatory nonshivering thermogenesis exits in adult man not acclimatized to cold, that it is mediated by noradrenaline, that the major fuel substrate for the increased energy demand is the triglycerides from the fat stores, and that the splanchnic area contributes only irregularly and to a small degree to this part of thermogenesis.

An assessment of human regulatory nonshivering thermogenesis.

To assess human thermoregulation independent of muscular activity, a method was developed exposing adult man not previously acclimatized to cold under simultaneous vasodilatation, resulting in a heat debt from the body. During exposure, a significant increase in oxygen consumption was found in two groups, the increases were 0.06 mmol . kg-1, . min-1 (41%) (range: 0.023--0.113) and 0.046 mmol . kg-1 . min-1 (30%) (range: --0.013--0.078), respectively. The change in plasma concentration of catecholamines showed a significant increase in noradrenaline of 4.58 nmol/l (300%) (range: 1.86--9.56), whereas adrenaline did not change measureably. The plasma concentration of non-esterified fatty acids (NEFA) showed a significant increase of 0.47 l mmol/l (96%) (range: 0.033 to 0.687), whereas the plasma concentration of glucose fell by only 0.3 mmol/l (6%) (range: 0.1--0.9). The results obtained by this method mirror findings from studies on small mammals acclimatized to cold, indicating that man without visible shivering and discomfort can increase heat production by an increased secretion of noradrenaline and by utilizing the fat stores in adipose tissue as the major substrate for this increased energy demand.

The cortisol fluctuations in plasma in relation to human regulatory nonshivering thermogenesis.

It is known that many stressful situations are accompanied by an increase in plasma cortisol concentration. This study was undertaken to see if a standardized and moderate exposure to cold under simultaneous peripheral vasodilation, which is known to result in increased oxygen consumption and plasma concentration of noradrenaline, can be considered a stress, based on changes in plasma cortisol concentration. Since the nonshivering thermogenesis induced is dependent on normal thyroid function, nine of the 19 adult humans exposed to cold were normo-, four hyper-, and six hypothyroid. The cold exposure was carried out in every case between 9 a.m. and 11 a.m. Since the cortisol secretion reflects the circadian cycle, a further six normothyroid persons were exposure to cold between 5 a.m. and 7 a.m. The exposure in this study does not reflect any stress condition, as the plasma cortisol concentration during the investigations between 9 a.m. and 11 a.m. decreased significantly by mean values of 0.1 mmol/l (29%) (range: -0.07--0.2 mmol/l) in the normothyroid group, by 0.23 mmol/l (68%) (range: 0.09--0.44 mmol/l) in the hyperthyroid group, and by 0.16 mmol/l (29%) (range: 0.03--0.38 mmol/l) in the hypothyroid group. The normothyroid persons investigated between 5 a.m. and 7 a.m. showed a significant fall similar to that mentioned above. The differences in the results obtained between the normo- and dysthyroid groups, before and during the exposure, merely reflected variations known from non-stressful conditions.

The relation between thyroid function and human regulatory nonshivering thermogenesis.

By a standardized exposure to cold air under simultaneous vasodilation, it was possible to elucidate the chemical factors responsible for heat production independent of muscular activity in seven patients with thyrotoxicosis and in nine patients with hypothyroidism. The results showed that hyperthryroid patients have a thermoregulatory reserve equal to normal persons, as they were able to increase their oxygen consumption significantly by an average of 0.035 mmol . kg-1 . min-1 (16%) (range: 0.014--0.064). The plasma concentration of non-esterified fatty acids (NEFA) increased significantly by an average of 0.675 mmol/l (64%) (range: 0.015--2.220). The hypothyroid patients also increased their oxygen consumption significantly by an average of 0.032 mmol . kg-1 . min-1 (30) (range: -0.016--0.066), but in this group the normal fat mobilization was inhibited as no rise in plasma NEFA was seen. Administration of exogenous thyroxine restored thermoregulation to the level and pattern seen in normothyroid persons, as the increase in plasma NEFA after treatment was on average 0.483 nnol/l (192%) (range: 0.342--0.733).

Cold thermogenesis in the summer-acclimatized and cold-acclimated domestic fowl

1. Summer-acclimatized and cold-acclimated fowls, saline or propranolol treated, were exposed to air temperatures between 25 and 2°C. 2. V dot o 2 on integrated EMG activity regression was linear; its intercept was higher in the cold acclimated fowls. 3.Propranolol markedly reduced shivering and V dot o 2 ; subsequently V dot o 2 recurred to normal with no change in EMG activity level in both groups. 4. These were interpreted to indicate the presence of obligatory non-shivering thermogenesis dependent on cold-acclimation and to suggest a possible capacity for regulatory non-shivering thermogenesis independent on cold-acclimation.

O2 transport and Vo2 in resting muscle: significance for tissue-capillary exchange.

O2 transport and Vo2 in resting muscle: significance for tissue-capillary exchange.