Effect of unilateral surgical denervation of brown adipose tissue on uncoupling protein mRNA level and cytochrom-c-oxidase activity in the Djungarian hamster

The bilateral lobe of interscapular brown adipose tissue of the Djungarian hamster was unilaterally denervated in order to study the role of the sympathetic innervation for maintenance and cold-induced increase of non-shivering thermogenesis. Denervation decreased the noradrenaline content of brown adipose tissue to less than 9% of the intact contralateral pad. This low noradrenaline level was maintained for 1–14 days after denervation. First, to study the role of the sympathetic innervation of brown adipose tissue in the maintenance of the high thermogenic capacity characteristic of the cold acclimated state, brown adipose tissue was denervated in hamsters either kept at thermoneutrality or acclimated to 5°C ambient temperature for 4 weeks. Cold-acclimated hamsters had elevated levels of uncoupling protein messenger ribonucleic acid (8.1-fold) and cytochrom-c oxidase-activity (3-fold). Denervation of brown adipose tissue decreased uncoupling protein-messenger ribonucleic acid level and cytochrom-c-oxidase-activity as compared to the intact pad in thermoneutral and in cold-acclimated hamsters. However, in cold-acclimated hamsters uncoupling protein-messenger ribonucleic acid level and cytochrom-c-oxidase-activity in denervated brown adipose tissue both were maintained on an elevated 6-fold higher levels as compared to thermoneutral controls. Second, to study the role of the sympathetic innervation of brown adipose tissue in the cold-induced increase in thermogenic capacity, hamsters were denervated prior to cold acclimation and responses were measured after 3 and 14 days of cold exposure. Uncoupling protein-messenger ribonucleic acid level and cytochrom-c-oxidase-activity of intact brown adipose tissue increased after 14 days cold acclimation. Denervation did not completely prevent a cold-induced 1.5-fold increase of cytochrom-c-oxidase-activity and a 3.2-fold increase of the uncoupling protein-messenger ribonucleic acid level in denervated brown adipose tissue after 14 days of cold acclimation. In conclusion, high levels of uncoupling protein-messenger ribonucleic acid and cytochrom-c-oxidase activity in brown adipose tissue of cold-acclimated hamsters can partially be maintained without intact sympathetic innervation, suggesting a considerable contribution of trophic factors not requiring sympathetic innervation for maintenance. The cold-induced increase of cytochrom-c-oxidase activity and expression of uncoupling protein-messenger ribonucleic acid largely depends upon sympathetic innervation of brown adipose tissue.Abbreviations ANOVA analysis of variance - BAT brown adipose tissue - COX cytochrom-c-oxidase - HPLC high performance liquid chromatography - mRNA messenger ribonucleie acid - NA noradrenaline - T _a ambient temperature - UCP uncoupling protein     

Effects of temperature and photoperiod on thermogenesis in plateau pikas (Ochotona curzoniae) and root voles (Microtus oeconomus)

We examined the effects of temperature and photoperiod on metabolic thermogenesis and the thermogenic characteristics of brown adipose tissue in plateau pikas (Ochotona curzoniae) and root voles (Microtus oeconomus), the dominant species of small mammals in the alpine meadow ecosystems on the Qinghai-Tibetan Plateau. Pikas and voles were acclimated in the following groups: (1) Long day – warm temperature (16L:8D, 23 °C), (2) Long day – cold temperature (16L:8D, 5 °C), (3) short day – warm temperature (8L:16D, 23 °C), and (4) short day – cold temperature (8L:16D, 5 °C). Both temperature and photoperiod were important environmental cues for changes in thermogenesis for both species. Low temperature and short photoperiod induced increases in metabolic rate, nonshivering thermogenesis (NST), mitochondrial protein contents of brown adipose tissue, and cytochrome C oxidase activity of brown adipose tissue mitochondria in both species. Plateau pikas were more sensitive to cold (79% of the total NST response) than to short photoperiod (21%), while root voles were more sensitive to short photoperiod (60% of the total NST response) than to cold (40%), although cold clearly enhanced thermogenesis. Their thermogenic characteristics correlated with their preferred habitats: plateau pikas are found mainly in more exposed microhabitats in open sunny meadow, while root voles live in more sheltered microhabitats in relatively closed shrub. Our results also showed that temperature and photoperiod combined induce thermogenic adjustments in both species in seasonal acclimatization in their alpine meadow macrohabitat. Accepted: 10 November 1998     

Photoperiod regulates leptin sensitivity in field voles, Microtus agrestis

We have previously shown that cold-acclimated (8°C) male field voles (Microtus agrestis) transferred from short (SD, 8:16 h L:D) to long photoperiod (LD, 16:8 h L:D) exhibit increases in body mass, adiposity and food intake. To assess whether these increases were associated with decreased leptin sensitivity, we infused LD and SD voles with physiological doses of murine leptin (or saline) delivered peripherally for 7 days via mini-osmotic pumps. Measurements were made of body mass (weight-reducing effect of leptin), food intake (anorectic effect of leptin) and gene expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) (thermogenic effect of leptin). The SD animals were sensitive to the weight-reducing effects of leptin (mean body mass decrease of 1.2 g over 7 days) and appetite-reducing effect of leptin (mean food intake decrease of 2.5 g over 7 days), whereas LD voles were resistant to the hormone treatment. The switch from a leptin-sensitive to leptin-resistant state appears to act as a desensitisation mechanism that allows voles transferred from SD to LD to ignore elevated leptin levels generated by increased body fat and accumulate adipose tissue without stimulating compensatory changes opposing the weight gain. Neither SD nor LD voles responded to infusion of leptin by changes in BAT UCP1 gene expression, suggesting dissociation of anorectic and thermogenic effects of leptin, possibly related to chronic cold exposure. Our results indicate that cold-acclimated voles show photoperiod-regulated changes in leptin sensitivity and may provide an attractive model for elucidating molecular mechanisms of leptin resistance.     

Thermogenic Ability of Uncoupling Protein 1 in Beige Adipocytes in Mice

Chronic adrenergic activation leads to the emergence of beige adipocytes in some depots of white adipose tissue in mice. Despite their morphological similarities to brown adipocytes and their expression of uncoupling protein 1 (UCP1), a thermogenic protein exclusively expressed in brown adipocytes, the beige adipocytes have a gene expression pattern distinct from that of brown adipocytes. However, it is unclear whether the thermogenic function of beige adipocytes is different from that of classical brown adipocytes existing in brown adipose tissue. To examine the thermogenic ability of UCP1 expressed in beige and brown adipocytes, the adipocytes were isolated from the fat depots of C57BL/6J mice housed at 24°C (control group) or 10°C (cold-acclimated group) for 3 weeks. Morphological and gene expression analyses revealed that the adipocytes isolated from brown adipose tissue of both the control and cold-acclimated groups consisted mainly of brown adipocytes. These brown adipocytes contained large amounts of UCP1 and increased their oxygen consumption when stimulated with norepinephirine. Adipocytes isolated from the perigonadal white adipose tissues of both groups and the inguinal white adipose tissue of the control group were white adipocytes that showed no increase in oxygen consumption after norepinephrine stimulation. Adipocytes isolated from the inguinal white adipose tissue of the cold-acclimated group were a mixture of white and beige adipocytes, which expressed UCP1 and increased their oxygen consumption in response to norepinephrine. The UCP1 content and thermogenic ability of beige adipocytes estimated on the basis of their abundance in the cell mixture were similar to those of brown adipocytes. These results revealed that the inducible beige adipocytes have potent thermogenic ability comparable to classical brown adipocytes.     

Sympathetic and adrenocorticoid influences on diet-induced thermogenesis and brown fat activity in the rat

Bilateral adrenalectomy markedly reduced body weight and energy gain and energetic efficiency of adult cafeteria-fed rats but enhanced the thermogenic response to food and stimulated brown fat activity. These changes were totally prevented by replacement of the animals with corticosterone (1 mg/rat/day). Unilateral denervation of the sympathetic nerves supplying the interscapular brown adipose tissue abolished the enhanced activity resulting from adrenalectomy and inhibited thermogenic activity in brown fat from cafeteria rats with intact adrenals, but had no effect in adrenalectomised animals treated with a high dose of corticosterone.     

Effect of photoperiod on body weight and food intake of obese and lean Zucker rats

Although the rat is usually not considered to be sensitive to photoperiod, under some experimental conditions photoperiod responses are unmasked. In addition, we have observed photoperiod-induced changes in body weight gain in lean and obese Zucker rats. In this experiment, body mass, food intake, body composition, brown adipose tissue (BAT) thermogenic state, and blood concentrations of corticosterone, insulin, and glucose were evaluated under one of two lighting conditions: a short (10 h light: 14 h dark) or a long (14 h light: 10 h dark) photoperiod. Plasma corticosterone and glucose concentrations measured under fasting conditions were unaffected by photoperiod in either genotype. The amount of BAT mitochondrial protein isolated was less in long photoperiod rats. BAT mitochondrial GDP binding was unaffected by photoperiod in the lean rats, but tended to be lower in long photoperiod obese rats than in short photoperiod obese rats. Although, photoperiod had no effect on daily food intake of rats exposed to the short versus long photoperiod, body mass was heaviest in obese rats raised in long photoperiod. Plasma insulin was increased in both lean and obese rats in long photoperiod. In addition, fat storage appeared to shift to internal depots in the lean rats exposed to long photoperiod. Our data demonstrate that photoperiod does have an effect on male Zucker rats with respect to body weight and fat distribution, with the obese rats being more sensitive to changes in photoperiod than the lean rats.     

Long photophase is not a sufficient stimulus to reduce thermogenic capacity in winter-acclimatized short-tailed field voles (Microtus agrestis) during long-term cold acclimation

The thermogenic capacity of brown adipose tissue in winter- and summer-acclimatized short-tailed field voles (Microtus agrestis) was investigated by examining changes in mass of brown adipose tissue, the ratio of white adipose tissue to brown adipose tissue, the concentration of the uncoupling protein (thermogenin) in whole depots (μg) and in mitochondrial mass (μg·mg^-1) and the activity of cytochrome c oxidase in the depots (mmol·min^-1). The concentration of thermogenin in winter-acclimatized voles (n=8), per brown adipose tissue depot and per mitochondrial mass, was significantly higher than in summer-acclimatized voles (n=6). There was no significant difference in the level of cytochrome c oxidase activity between these two groups. Four groups of winter-acclimatized voles (n=6 in each group) were exposed to 5°C for 10, 20, 50 and 100 days in a 14L:10D photoperiod. Body mass, brown adipose tissue mass, white adipose tissue mass and basal metabolic rate were significantly positively related to the length of time cold exposed up to 100 days. There was a significant inverse relationship between the ratio of white to brown adipose tissue mass and the duration of cold exposure. There was no significant relationship between thermogenin concentration, either per depot or in mitochondrial mass of brown adipose tissue, with the length of time cold exposed. The level of cytochrome c oxidase activity increased significantly from control levels to a maximum after 10 days in the cold but decreased from 10 days onwards. In winter-acclimatized M. agrestis, a 14L:10D photoperiod is not a sufficient stimulus to reduce thermogenic capacity during cold acclimation. Indeed, some changes in the indirect parameters reflecting thermogenesis, notably the increase in basal metabolic rate and the decrease in the ratio of white to brown adipose tissue mass, indicated that despite the long photophase the thermogenic capacity was slightly further enhanced during the cold acclimation.     

Characteristics of beta-adrenergic receptors in isolated cells and in crude membranes of brown adipose tissue

In relation to decreased metabolic sensitivity to catecholamines observed, in vitro, in brown fat of cold-acclimated rats, beta-adrenergic receptors were studied in isolated cells and in a crude membrane preparation from rat interscapular brown adipose tissue. [3H] dihydroalprenolol binding had the same characteristics in both types of preparation; competition studies of [3H] dihydroalprenolol binding led to the characterization of beta 1 subtype adrenergic receptors with a lower affinity of beta-adrenergic agonists for [3H] dihydroalprenolol binding sites in membranes than that found in isolated cells. Cold acclimation produced, in isolated cells only, a decrease of 41% in the [3H] dihydroalprenolol binding sites and a beta-adrenergic agonist affinity increase. It is concluded that beta-adrenergic receptor decrease could be a factor, at the hormone receptor interaction level, in the regulation of the transmission of biological action responsible for the cold-induced decrease in catecholamine responsiveness in brown adipose tissue. For a study of the desensitization process in brown fat, isolated cells seem to offer certain advantages over a crude membrane preparation.     

光照和温度对根田鼠褐色脂肪组织产热能力的影响

测定了根田鼠在室内驯化2周后褐色脂肪组织（BAT）的蛋白含量、线粒体蛋白含量和细胞色素C氧化酶活性的变化。动物进行如下4种处理:23℃,16L:8D;23℃,8L：16D;5℃,16L：8D和5℃,8L:16D.。结果表明,短光照可刺激根田鼠的BAT线粒体细胞色素C氧化酶的活性增加;低温驯化可导致根田鼠的BAT线粒体蛋白含量增加;短光照加低温可进一步促进酶的活性增加。结合个体水平的产热特点,说明根田鼠在产热能力的季节驯化过程中,光周期是一主要的季节调节信号,环境温度进一步增强光照的作用,环境温度和光周期共同作用以诱导其产热能力等方面的生理调节。研究结果支持了环境温度和光周期共同作用以调节动物产热变化的学说。     

Photoperiodic regulation in energy intake, thermogenesis and body mass in root voles (Microtus oeconomus)

The present study was designed to examine whether photoperiod alone was effective to induce seasonal regulations in physiology in root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau noted for its extreme cold environment. Root voles were randomly assigned into either long photoperiod (LD; 16L:8D) or short photoperiod (SD; 8L:16D) for 4 weeks at constant temperature (20 degrees C). At the end of acclimation, SD voles showed lower body mass and body fat coupled with higher energy intake than LD voles. SD greatly enhanced thermogenic capacities in root voles, as indicated by elevated basal metabolic rate (BMR), nonshivering thermogenesis (NST), mitochondrial protein content and uncoupling protein-1 (UCP1) content in brown adipose tissue (BAT). Although no variations in serum leptin levels were found between SD and LD voles, serum leptin levels were positively correlated with body mass and body fat mass, and negatively correlated with energy intake and UCP1 content in BAT, respectively. To summarize, SD alone is effective in inducing higher thermogenic capacities and energy intake coupled with lower body mass and body fat mass in root voles. Leptin is potentially involved in the photoperiod induced body mass regulation and thermogenesis in root voles.     

Iodothyronine 5'-deiodinase activity in rat brown adipose tissue during development

Iodothyronine 5'-deiodinase activity in rat brown adipose tissue has a characteristic pattern of developmental changes that is completely different from that of the liver. Fetal brown fat exhibits an extremely high iodothyronine 5'-deiodinase activity that is approx. 10-fold that in adult rats. Even though brown fat iodothyronine 5'-deiodinase activity falls suddenly at birth, there is a new peak in the activity around days 5-7 of life, whereas it remains very low afterwards. Just after birth, brown adipose tissue iodothyronine 5'-deiodinase activity is already capable of stimulation by noradrenaline. The postnatal peak in brown fat iodothyronine 5'-deiodinase correlates with the known increase in the thermogenic activity of the tissue in the neonatal rat, thus reinforcing the suggestion that local 3',3,5-triiodothyronine generation could be an important event related to thermogenesis in brown adipose tissue. However, the high fetal activity was only slightly related to the thermogenic activity of brown fat. Moreover, the increased iodothyronine 5'-deiodinase activity of brown adipose tissue during fetal and neonatal life suggests a substantial contribution by brown fat in the overall extrathyroidal 3',3,5-triiodothyronine production in these physiological periods.     

Absence of adaptive nonshivering thermogenesis in a marsupial,the fat-tailed dunnart (<Emphasis Type="Italic">Sminthopsis crassicaudata</Emphasis>)

The presence of nonshivering thermogenesis in marsupials is controversially debated. Survival of small eutherian species in cold environments is crucially dependent on uncoupling protein 1 (UCP1)-mediated, adaptive nonshivering thermogenesis that is executed in brown adipose tissue. In a small dasyurid marsupial species, the fat-tailed dunnart (Sminthopsis crassicaudata), an orthologue of UCP1 has been recently identified which is upregulated during cold exposure resembling adaptive molecular adjustments of eutherian brown adipose tissue. Here, we tested for a thermogenic function of marsupial brown adipose tissue and UCP1 by evaluating the capacity of nonshivering thermogenesis in cold-acclimated dunnarts. In response to an optimal dosage of noradrenaline, cold-acclimated dunnarts (12°C) showed no additional recruitment of noradrenaline-induced maximal thermogenic capacity in comparison to warm-acclimated dunnarts (24°C). While no differences in body temperature were observed between the acclimation groups, basal metabolic rate was significantly elevated after cold acclimation. Therefore, we suggest that adaptive nonshivering thermogenesis does not occur in this marsupial species despite the cold recruitment of oxidative capacity and UCP1 in the interscapular fat deposit. In conclusion, the ancient UCP orthologue in marsupials does not contribute to the classical nonshivering thermogenesis, and may exhibit a different physiological role.     

Effects of photoperiod on energy intake, thermogenesis and body mass in Eothenomys miletus in Hengduan Mountain region

The present study was designed to examine whether photoperiod alone was effective to induce seasonal changes in physiology in voles (Eothenomys.) from the Hengduan Mountain region. Eothenomys miletus were randomly assigned into either long photoperiod (LD; 16L: 8D) or short photoperiod (SD; 8L: 16D) for 4 weeks at constant temperature (25 °C). At the end of acclimation, SD voles showed lower body mass and body fat coupled with higher energy intake than LD voles. SD greatly enhanced the thermogenic capacity of E. miletus, as indicated by an elevated nonshivering thermogenesis (NST), mitochondrial protein in brown adipose tissue (BAT); basal metabolic rate (BMR) was also raised. Although no variations in serum leptin levels were found between SD and LD voles, serum leptin levels were positively correlated with body mass and body fat mass, and negatively correlated with energy intake and UCP1 content in BAT, respectively. To summarize, SD alone is effective in inducing higher thermogenic capacities and energy intake coupled with lower body mass and body fat mass in root voles. Leptin is potentially involved in the photoperiod induced body mass regulation and thermogenesis in E. miletus. Our study shows that SD alone is effective.     

Impaired basal and noradrenaline-induced iodothyronine 5'-deiodinase activity in brown adipose tissue from pregnant and lactating rats

Basal iodothyronine 5'-deiodinase activity is lowered in brown fat from 20-day pregnant, 5 and 15-day lactating rats when compared with virgin controls. Acute noradrenaline treatment caused a seven fold increase in 5'-deiodinase activity in brown fat from virgin control rats. Late pregnant and lactating rats showed a reduction in noradrenaline-induced 5'-deiodinase activity in brown adipose tissue and the maximum impairment was observed in 15-day lactating rats. Lowered 5'-deiodinase activity in brown fat during late pregnancy and lactation correlates with the known reduction in the thermogenic activity of the tissue during these situations and agrees with the proposal that the rate of 3,5,3'-triiodothyronine generated in situ because of thyroxine 5'-deiodination could be an essential event related to thermogenesis in brown fat. Even though the relationship between 3,5,3'-triiodothyronine generation in the tissue and the specific thermogenic mechanisms of brown fat is unknown, present results indicate a close link between the thermogenic and 5'-deiodinase activities in physiological situations when brown adipose tissue needs to adapt to a low activity, such as that of the breeding cycle.     

Iodothyronine 5′-deiodinase activity in rat brown adipose tissue during development

Iosothyronine 5′-deiodinase activity in rat brown adipose tissue has a characteristic pattern of developmental changes that is completely different from that of the liver. Fetal brown fat exhibits an extremely high iodothyronine 5′-deiodinase activity that is approx. 10-fold that in adult rats. Even though brown fat iodothyronine 5′-deiodinase activity falls suddenly at birth, there is a new peak in the activity around days 5–7 of life, whereas it remaines very low afterwards. Just after birth, brown adipose tissue iodothyronine 5′-deiodinase activity is already capable of stimulation by noradrenaline. The postnatal peak in brown fat iodothyronine 5′-deiodinase correlates with the known increase in the thermogenic activity of the tissue in the neonatal rat, thus reinforcing the suggestion that local 3′,3,5-triiodothyronine generation could be an important event related to thermogeneis in brown adispose tissue. However, the high fetal activity was only slightly related to the thermogenic activity of brown fat. Moreover, the increased iodothyronine 5′-deiodinase activity of brown adipose tissue during fetal and neonatal life suggests a substantial contribution by brown fat in the overall extrahydroidal 3′,3,5-triiodothyronine production in these physiological periods.     

Effects of photoperiod, melatonin, and the pineal gland on compensatory gonadal hypertrophy during postnatal development in the marsh rice rat (Oryzomys palustris)

The roles of photoperiod, melatonin, and the pineal gland in regulating the magnitude of compensatory gonadal hypertrophy (CGH) and other reproductive and non-reproductive organ growth during post-weaning development were examined in the marsh rice rat Oryzomys palustris. Juvenile rice rats of both sexes were left gonadally intact (control group) or unilaterally castrated (ULC) and housed on 12L:12D, 14L:10D, or 16L:8D. Within a photoperiod (14L:10D and 16L:8D, but not 12L:12D), growth of the remaining testis, but not the remaining ovary, as well as several additional organs in both sexes were significantly affected, suggesting that the compensatory hypertrophy of the testis is photoperiod-dependent. There was no effect of testis asymmetry on CGH as ULC of either testis in rice rats housed on 14L:10D resulted in a comparable increase of CGH. Melatonin implants in rice rats maintained on 16L:8D had little to no effect (CGH included) on most parameters examined. Both melatonin implants and pinealectomy (separate experiments) in rice rats transferred to 12L:12D prevented short photoperiod-induced effects on CGH, the growth of the reproductive organs and the Harderian glands. Evening melatonin injections had a significant inhibitory effect on the growth of the remaining testis (no CGH was observed) and all other parameters measured. Lastly, ULC did not alter the percentage of males which successfully mated compared to intact animals. Taken together, these data suggest that photoperiod, melatonin, and the pineal gland can affect and regulate reproductive (e.g., CGH in some cases) and non-reproductive growth during postnatal development in the marsh rice rat.     

Cold acclimation and oxygen consumption in the thymus

Mitochondrial uncoupling protein 1 is usually associated with brown adipose tissue but has recently been discovered in rat and mouse thymus. We wished to establish whether there was a thermogenic role for UCP 1 in thymus and thus examined the effect of 5 weeks cold-acclimation on rat thymus tissue abundance, thymocyte oxygen consumption, thymus mitochondrial abundance, uncoupling protein 1 expression and function. We found that thymocytes from cold-acclimated rats had oxygen consumption rates 8 times less than those from rats held at room temperature and that thymocytes from cold-acclimated rats or rats kept at room temperature were noradrenaline insensitive. In addition, we found that thymus tissue or mitochondrial abundance was not increased after cold-acclimation. However uncoupling protein 1 expression per unit mass of mitochondria was increased after cold-acclimation, as determined by immunoblotting (approximately 1.7-fold) and GDP binding (approximately 1.5-fold). Consistent with our protein expression data, we also observed an increased, state 4 (approximately 1.5-fold), GDP-inhibitable (approximately 1.3-fold) and palmitate activatable (approximately 1.6-fold) oxygen consumption rates in isolated thymus mitochondria. However, extrapolation of our data showed that cold-acclimation only increased the amount of UCP 1 per gram of thymus tissue approximately 1.2-fold. Taken together, we conclude that UCP 1 does not have a thermogenic role in thymus.     

Sympathetically mediated hypermetabolic response to cerebral ischemia in the rat

Cerebral ischemia, induced in rats by occlusion of the middle cerebral artery resulted in infarcts affecting the basal ganglia and adjacent frontoparietal cortex. Resting oxygen consumption was similar for sham-operated and ischaemic rats immediately after surgery but was elevated in the latter group (peak value 18-21% above controls) 5-6 h post occlusion. By 24 h, these values had returned to control levels. The increase in VO2 was inhibited by injection of the beta-adrenergic antagonist propranolol but was unaffected by injection of the cyclooxygenase inhibitor ibuprofen. The thermogenic activity of brown adipose tissue was assessed from in vitro binding of guanosine diphosphate to mitochondria isolated from intact and surgically denervated lobes of sham-operated and ischemic rats, 6 h after surgery. Brown adipose tissue specific guanosine diphosphate (GDP) binding was elevated by 86% in intact tissue from ischemic compared with sham-operated rats but was identical in denervated tissue from the two groups. Brown adipose tissue activity correlated with resting oxygen consumption in the ischemic group (r = 0.85, p less than 0.01) but not in controls (r = -0.35, NS). Thus occlusion of the middle cerebral artery in the rat may provide a representative model for both stroke and head injury in man. It is associated with a transient increase in metabolic rate and by sympathetically mediated activation of brown adipose tissue in the rat.     

Plasma free fatty acid levels during cold-induced and noradrenaline-induced nonshivering thermogenesis in the Djungarian hamster

Summary In Djungarian hamsters the cold-induced thermoregulatory heat production was preceeded and accompanied by an increase in the plasma level of free fatty acids. In warm-acclimated hamsters this increase was found more pronounced (0.85 to 1.48 mM) than in cold-acclimated hamsters (0.64 to 0.88 mM). Noradrenaline-induced thermogenesis at thermoneutrality provoked a similar increase in the free fatty acid level. Inhibition of nonshivering thermogenesis during cold exposure by propranolol abolished the increase in free fatty acids completely. The surgical removal of brown adipose tissue proportionately reduced the increase in free fatty acids. This indicates that the rise in plasma free fatty acids is functionally related to nonshivering thermogenesis and originates from brown adipose tissue.     

Mitochondrial respiration in muscle and liver from cold-acclimated hypothyroid rats.

The effects of long-term cold exposure on muscle and liver mitochondrial oxygen consumption in hypothyroid and normal rats were examined. Thyroid ablation was performed after 8-wk acclimation to 4 degrees C. Hypothyroid and normal controls remained in the cold for an additional 8 wk. At the end of 16-wk cold exposure, all hypothyroid rats were alive and normothermic and had normal body weight. At ambient temperature (24 degrees C), thyroid ablation induced a 65% fall in muscle mitochondrial oxygen consumption, which was reversed by thyroxine but not by norepinephrine administration. After cold acclimation was reached, suppression of thyroid function reduced muscle mitochondrial respiration by 30%, but the hypothyroid values remained about threefold higher than those in hypothyroid muscle in the warm. Blockade of beta- and alpha1-adrenergic receptors in both hypothyroid and normal rats produced hypothermia in vivo and a fall in muscle, liver, and brown adipose tissue mitochondria respiration in vitro. In normal rats, cold acclimation enhanced muscle respiration by 35%, in liver 18%, and in brown adipose tissue 450% over values in the warm. The results demonstrate that thyroid hormones, in the presence of norepinephrine, are major determinants of thermogenic activity in muscle and liver of cold-acclimated rats. After thyroid ablation, cold-induced nonshivering thermogenesis replaced 3,5,3'-triiodothyronine-induced thermogenesis, and normal body temperature was maintained.