Amount Of Brown Adipose Tissue Research Articles

Fetal and Neonatal Thermoregulation

The metabolic rate of the fetus per tissue weight is relatively high when compared to that of an adult. Moreover, heat is transferred to the fetus via the placenta and the uterus, resulting in a 0.3 degrees C to 0.5 degrees C higher temperature than that of the mother. Therefore, fetal temperature is maternally dependent until birth. At birth, the neonate rapidly cools in response to the relatively cold extrauterine environment. Thus, the neonatal temperature rapidly drops soon after birth. In order to survive, the neonate must accelerate heat production via nonshivering thermogenesis (NST), which is coupled to lypolysis in brown adipose tissue. Heat is produced by uncoupling ATP synthesis via the oxidation of fatty acids in the mitochondria, utilizing uncoupled protein. Thermogenesis must begin shortly after birth and continue for several hours. Since thermogenesis requires adequate oxygenation, a distressed neonate with hypoxemia cannot produce an adequate amount of heat to increase its temperature. In contrast to the neonate, the fetus cannot produce extra heat production. This is because the fetus is exposed to inhibitors to NST, which are produced in the placenta and then enter the fetal circulation. The important inhibitors include adenosine and prostaglandin E2, both of which have strong anti-lypolytic actions. The inhibitors play an important role in the metabolic adaptation of a physiological hypoxic fetus because NST requires adequate oxygenation. Furthermore, the presence of NST inhibitors allows the fetus to accumulate an adequate amount of brown adipose tissue before birth. The umbilical circulation transfers 85% of the heat produced by the fetus to the maternal circulation. The remaining 15% is dissipated through the fetal skin to the amnion, and is then transferred through the uterine wall to the maternal abdomen. As long as fetal heat production and loss are appropriately balanced, the temperature differential between the fetus and the mother remains constant (heat clump). However, when the umbilical circulation is occluded for any reason, the fetal temperature will rise in relation to the extent of the occlusion. The fetal temperature may elevate to the hyperthermic range in cases of acute cord occlusion; if this occurs, fetal growth, including brain development, may be impacted. Experimentally induced cord occlusion, which is recognized as a significant cause of brain damage, results in a rapid elevation of body temperature; however, the brain temperature tends to remain constant. This is considered to be a cerebral thermoregulatory adaptation to hypoxemia, which has the physiologic advantage of protecting the fetus from hyperthermia, a condition that predisposes the fetus to hypoxic injury (cerebral hypometabolism). A number of thermoregularatory mechanisms are in place to maintain normal fetal and neonatal growth. Data has primarily been collected from animal studies; aside from the strict thermal control provided in the newborn nursery, little information exists concerning these mechanisms in the human fetus and neonate. Probably further information on thermoregulation is necessary specially to improve perinatal management for hypoxic fetuses.

Hyperleptinemia, Visceral Adiposity, and Decreased Glucose Tolerance in Mice with a Targeted Disruption of the Histidine Decarboxylase Gene

Histamine has been referred to as an anorexic factor that decreases appetite and fat accumulation and affects feeding behavior. Tuberomammillary histaminergic neurons have been implicated in central mediation of peripheral metabolic signals such as leptin, and centrally released histamine inhibits ob gene expression. Here we have characterized the metabolic phenotype of mice that completely lack the ability to produce histamine because of targeted disruption of the key enzyme in histamine biosynthesis (histidine decarboxylase, HDC). Histochemical analyses confirmed the lack of HDC mRNA, histamine immunoreactivity, and histaminergic innervation throughout the brain of gene knockout mouse. Aged histamine-deficient (HDC-/-) mice are characterized by visceral adiposity, increased amount of brown adipose tissue, impaired glucose tolerance, hyperinsulinemia, and hyperleptinemia. Histamine-deficient animals are not hyperphagic but gain more weight and are calorically more efficient than wild-type controls. These metabolic changes presumably are due to the impaired regulatory loop between leptin and hypothalamic histamine that results in orexigenic dominance through decreased energy expenditure, attenuated ability to induce uncoupling protein-1 mRNA in the brown adipose tissue and defect in mobilizing energy stores. Our results further support the role of histamine in regulation of energy homeostasis.

Unexpected deposition of brown fat in mammary gland during postnatal development.

Mammary fat tissue is crucial for mammary ductal morphogenesis in both fetal and adult mice. There are two kinds of adipocytes, the energy-storing white and the energy-dissipating brown adipocyte. The precise identity of the types of adipocyte in the mammary gland has never been investigated but was always assumed to be only white fat. In this study, we show that both white and brown adipocytes are present in the postnatal mammary gland. The amount of brown adipose tissue (BAT) examined by histology and electron microscopy correlates with the transcript levels of uncoupling protein 1, which is a mitochondrial carrier expressed exclusively in BAT. Uncoupling protein 1 mRNAs are the highest during prepuberty, decrease upon puberty, and are finally undetectable in the adult mammary gland. The analysis of a BAT-depleted mouse model showed that depletion of mammary BAT in early postnatal development induces epithelial differentiation. Alveolar structures were formed along all ducts and were functional since they produced beta-casein. However, mammary transplantation experiments indicated that a systemic effect was responsible for epithelium differentiation. Our data suggest that BAT negatively regulates the differentiation of mammary epithelial cells in a systemic manner during prepubertal ductal outgrowth.

A new thiazolidinedione, NC-2100, which is a weak PPAR-gamma activator, exhibits potent antidiabetic effects and induces uncoupling protein 1 in white adipose tissue of KKAy obese mice.

Thiazolidinediones (TZDs) reduce insulin resistance in type 2 diabetes by increasing peripheral uptake of glucose, and they bind to and activate the transcriptional factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Studies have suggested that TZD-induced activation of PPAR-gamma correlates with antidiabetic action, but the mechanism by which the activated PPAR-gamma is involved in reducing insulin resistance is not known. To examine whether activation of PPAR-gamma directly correlates with antidiabetic activities, we compared the effects of 4 TZDs (troglitazone, pioglitazone, BRL-49653, and a new derivative, NC-2100) on the activation of PPAR-gamma in a reporter assay, transcription of the target genes, adipogenesis, plasma glucose and triglyceride levels, and body weight using obese KKAy mice. There were 10- to 30-fold higher concentrations of NC-2100 required for maximal activation of PPAR-gamma in a reporter assay system, and only high concentrations of NC-2100 weakly induced transcription of the PPAR-gamma but not PPAR-alpha target genes in a whole mouse and adipogenesis of cultured 3T3L1 cells, which indicates that NC-2100 is a weak PPAR-gamma activator. However, low concentrations of NC-2100 efficiently lowered plasma glucose levels in KKAy obese mice. These results strongly suggest that TZD-induced activation of PPAR-gamma does not directly correlate with antidiabetic (glucose-lowering) action. Furthermore, NC-2100 caused the smallest body weight increase of the 4 TZDs, which may be partly explained by the finding that NC-2100 efficiently induces uncoupling protein (UCP)-2 mRNA and significantly induces UCP1 mRNA in white adipose tissue (WAT). NC-2100 induced UCP1 efficiently in mesenteric WAT and less efficiently in subcutaneous WAT, although pioglitazone and troglitazone also slightly induced UCP1 only in mesenteric WAT. These characteristics of NC-2100 should be beneficial for humans with limited amounts of brown adipose tissue.

Life without white fat: a transgenic mouse.

We have generated a transgenic mouse with no white fat tissue throughout life. These mice express a dominant-negative protein, termed A-ZIP/F, under the control of the adipose-specific aP2 enhancer/promoter. This protein prevents the DNA binding of B-ZIP transcription factors of both the C/EBP and Jun families. The transgenic mice (named A-ZIP/F-1) have no white adipose tissue and dramatically reduced amounts of brown adipose tissue, which is inactive. They are initially growth delayed, but by week 12, surpass their littermates in weight. The mice eat, drink, and urinate copiously, have decreased fecundity, premature death, and frequently die after anesthesia. The physiological consequences of having no white fat tissue are profound. The liver is engorged with lipid, and the internal organs are enlarged. The mice are diabetic, with reduced leptin (20-fold) and elevated serum glucose (3-fold), insulin (50- to 400-fold), free fatty acids (2-fold), and triglycerides (3- to 5-fold). The A-ZIP/F-1 phenotype suggests a mouse model for the human disease lipoatrophic diabetes (Seip-Berardinelli syndrome), indicating that the lack of fat can cause diabetes. The myriad of consequences of having no fat throughout development can be addressed with this model.

Brown adipose tissue. More than an effector of thermogenesis?

Brown adipose tissue (BAT) produces heat by oxidation of fatty acids. This takes place when the tissue is stimulated by norepinephrine; the molecular background for the ability of BAT to produce heat is the tissue-specific mitochondrial protein UCP1. In the classic view of BAT with respect to fever, BAT is an effector organ, producing heat especially during the onset phase of the fever. There is good evidence that BAT thermogenesis is stimulated via a lipopolysaccharide (LPS), interleukin (IL)-1 beta, IL-6, prostaglandin E cascade. Under physiologic conditions of constantly stimulated activity, BAT is expected to be recruited, but in fevers this is only evident in thyroxine fever. However, BAT may be more than merely an effector. There are indications of a correlation between the amount of BAT and the intensity of fevers, and brown adipocytes can indeed produce IL-1 alpha and IL-6. Furthermore, brown adipocytes are directly sensitive to LPS; this LPS sensitivity is augmented in brown adipocytes from IL-1 beta-deficient mice. Thus, BAT may also have a controlling role in thermoregulation. The existence of transgenic mice with ablations of proteins central in fever and in BAT thermogenesis opens up possibilities for identification and elucidation of this putative new role for brown adipose tissue as an endocrine organ involved in the control of fever.

Localization, cellular morphology and respiratory capacity of “brown” adipose tissue in newborn reindeer

1. 1. The localization and cellular morphology of adipose tissue was studied by light, fluorescence and electron microscopy in reindeer between 2 weeks pre partum and 4.5 months post partum during calving, and the subsequent growth period. The respiratory capacity of the adipose tissue was examined in terms of morphometric mitochondrial volume and cytochrome- c oxidase or succinate dehydrogenase activity. 2. 2. Adipose tissue was located at specific anatomical sites in the newborn reindeer (from 0 to 2 days of age). The perirenal-abdominal depot was the largest location (32%) followed by the inter(pre)scapular (18%) and sternal (12%) depots. Internal depots dominated over external or peripheral depots (66-34%). The locations of adipose tissue were largely similar in foetal, newborn and young reindeer. 3. 3. The adipose tissue of the newborn reindeer had all the typical cell morphological characteristics of brown adipose tissue: abundant mitochondria, multilocular fat, high vascularization and a dense spot-like sympathetic innervation between the adipocytes. In the young reindeer, however, it resembled white adipose tissue, being almost totally unilocular with few mitochondria. 4. 4. There was a significant correlation between morphometric mitochondrial volume and cytochrome-c oxidase activity ( r = 0.848) in the adipose tissue. Mitochondrial volume, cytochrome- c oxidase and succinate dehydrogenase activity were highest after birth and decreased to almost an undetectable level during the first month. A parallel decrease occurred in the amount of brown adipose tissue from birth (1–2%) to the age of about one month (0.3%). 5. 5. It is concluded that the distinct cell morphological features and high respiratory capacity of the adipose tissue indicate the presence of brown adipose tissue at specific anatomical locations in newborn reindeer. A marked progression towards the characteristics of white adipose tissue then takes place at the same locations during the first month. The results suggest the fundamental significance of brown adipose tissue for non-shivering thennogenesis in newborn reindeer.

Seasonal variations in the lipid composition of white and brown tissues in the bat Pipistrellus pipistrellus

1. 1. Both sexes from Pipistrellus pipistrellus show changes in body weight, which was higher in the cold season. 2. 2. Sexual dimorphism was observed in white adipose tissue weight. 3. 3. Animals from the cold season had a greater amount of brown adipose tissue. 4. 4. No sexual differences were observed in the phospholipid and fatty acid compositions of white and brown tissues, although total phospholipids increased during the cold season in the latter tissue. 5. 5. Both tissues show a higher proportion of unsaturated to saturated fatty acids in the two seasons studied.

Age-associated decrease in beta-adrenergic receptors and adenylate cyclase activity in rat brown adipose tissue.

The ability to regulate body temperature diminishes with age. In the rat, nonshivering thermogenesis in brown adipose tissue (BAT) serves as the regulator of body temperature. This process is stimulated by catecholamine activation of adenylate cyclase through the beta-adrenergic receptor. However, beta-adrenergic responsiveness also diminishes with age. To investigate the age-related alterations in beta-adrenergic function in BAT, beta-adrenergic receptor number and cytochrome c oxidase activity were assessed in 3-, 12-, and 24-month-old rats, and adenylate cyclase activity was assessed in 3-, 12-, 18-, and 24-month-old rats. The amount of brown adipose tissue recovered from senescent rats was 30% less than that from either the 3- or 12-month-old rats. There was a corresponding decrease in the total amount of cytochrome c oxidase activity in the 24-month-old rats. In the senescent rats, the density of beta-adrenergic receptors was twofold less than in the 3- and 12-month-old rats. The decrease in density was predominately due to a decrease in the beta 1-adrenergic subtype. Isoproterenol- and NaF-stimulated adenylate cyclase activity were threefold greater and forskolin-stimulated activity was fourfold greater in the 3-month than in the older rats. There was no change in the Kact for isoproterenol with age. These biochemical alterations with age may contribute to the inability of older animals to thermoregulate when exposed to cold.

A 24-hour fast-induced loss of energetic substrates in the interscapular brown adipose tissue of ‘cafeteria’ rats

The incorporation of tracer-labelled glucose and alanine, as well as the levels of energetic components in interscapular brown adipose tissue of male rats fed either standard or ‘cafeteria’ diet have been studied in fed and 24-hour of food withdrawal situations. The relative amount of brown adipose tissue in cafeteria fed rats was much greater than in controls, whose size and composition were not altered with food withdrawal. Cafeteria fed rats lost significant amounts of both lipid and protein during food withdrawal. Label incorporation was comparable for glucose and alanine except within the lipidic fraction, in which cafeteria fed rats showed a considerably lower efficiency. The loss of protein with food withdrawal and the swift incorporation of alanine into protein, tissue amino acid pools and lipids suggest an easy utilization of these amino acids by both groups of rats. In addition, the loss of energetic substrates observed in the cafeteria fed rats during food withdrawal suggests a continued utilization of energetic substrates by this brown adipose tissue, a condition not observed in the tighter energetic budget of control rats.

Modes of thermal protection in newborn muskoxen (Ovibos moschatus).

The muskoxen (Ovibos moschatus), a native of Greenland and the Canadian North West Territories, give birth in late April, and the newborn calves are known to tolerate an ambient temperature (Ta) of -35 degrees C. At birth the calves weigh about 8 kg, increasing in weight with 0.6 kg . day-1 for the first 30 days. With a deep body temperature (DBT) of 39.5 degrees C (range 37.7-41.3 degrees C) the newborn calves are consequently able to maintain a thermogradient of at least 70 degrees C between body core and the environment. The calves use primarily two modes of thermal protection: High metabolic heat production and prime fur insulation. Metabolic rate was about 3.5 W . kg-1 at thermoneutrality in calves aged from 8 h to 7 days. Lower critical temperature at this age was about -7 degrees C and a drop in Ta to -30 degrees C increased metabolism to about 5.3 W . kg-1. Upper critical temperature at age 4-7 days is as low as 20 degrees C, while it in calves aged only 18-24 h appears to be even lower. The calves possess great amounts of brown adipose tissue (BAT) at birth. Mitochondria from the BAT deposits were isolated and found to be in an extremely loose-coupled state with a great capacity for thermogenesis. Skeletal muscle contained very few mitochondria and is hardly employed in aerobic non-shivering thermogenesis. Calves shiver visibly while drying just after birth, but are normally not seen shivering thereafter. The conductance value for the dry pelt of newborn calves averaged 3.2 W . m-2 . 0 degrees C-1 (n = 4). Wetting of the pelt with ice-water at a Ta of 3 degrees C increased conductance to 8.8 W . m-2 . 0 degrees C-1. The conductance of the pelt was also influenced by wind, being 10 W . m-2 . C-1 at a wind-speed of 10 m . sec-1. The legs of the newborn calves are heavily furred and countercurrent circulation is not present, subcutaneous temperature just above the hooves being +29.8 degrees C at Ta of -24 degrees C as compared to 37.5 degrees C on the back. The newborn calves could cope with a Ta of -30 degrees C without apparent problems under experimental conditions, but they suffered hypothermia when exposed to a Ta of -33 degrees C in combination with wind of 10 m . sec-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Trophic response of hamster brown adipose tissue: roles of norepinephrine and pineal gland.

The objective was to find out whether the reduced amount of brown adipose tissue in myopathic hamsters [Am. J. Physiol. 239 (Cell Physiol. 8): C18-C22, 1980] was secondary to a refractoriness to the trophic influence of norepinephrine. However, no evidence for any trophic influence of norepinephrine on brown adipose tissue of either normal or myopathic hamsters could be detected under experimental conditions that have demonstrated such an influence in rats. A mediator other than norepinephrine, melatonin, secreted by the pineal gland, is known to mediate the control of brown adipose tissue growth induced in hamsters by short photoperiod. Further studies of intact or pinealectomized hamsters showed that the pineal gland was not required for either cold- or diet-induced growth of brown adipose tissue. It is concluded that the defect in control of brown adipose tissue size in the hamster with muscular dystrophy is not due either to abnormal control by norepinephrine or to the pineal gland since neither of these appears to participate in the normal regulation of brown adipose tissue size in relation to environmental temperature or to diet.

Defective trophic response of brown adipose tissue of myopathic hamsters.

Hamsters with muscular dystrophy (BIO 14.6) have a smaller than normal amount of brown adipose tissue. Two stimuli that promote growth of brown adipose tissue in normal hamsters, short photoperiod and eating a high-fat diet, are here shown to be without effect on brown adipose tissue of myopathic hamsters. Cold-induced growth of brown adipose tissue occurs normally [Am. J. Physiol. 239 (Cell Physiol. 8): C18-C22, 1980]. There is a normal rate of turnover of norepinephrine in brown adipose tissue of the myopathic hamster but a failure of the tissue to hypertrophy in response to norepinephrine is unlikely since norepinephrine does not appear to mediate the trophic response [Am. J. Physiol. 247 (Endocrinol. Metab. 10): E793-E799, 1984]. Denervation results in a marked reduction in size (protein content) of brown adipose tissue of normal hamsters but has very little effect on the size of brown adipose tissue of myopathic hamsters. A central, possibly hypothalamic, defect in the myopathic hamster is postulated to underlie its abnormal control of brown adipose tissue hypertrophy.

Aspects of temperature regulation in mice selected for large and small size

SUMMARYWe measured traits involved in physiological and behavioural thermoregulation in the 6 replicates of a selection experiment for large and small size (6-week weight) in mice, including control lines (18 lines in all). The observed genetic correlations between body size and thermoregulatory traits are consistent with a thermoregulatory advantage of large size, including decreased weight-specific food consumption and increased nest-building, with no change in body temperature. The differences in food consumption were closely paralleled by differences in amount of brown adipose tissue, strongly suggesting that much of the decreased efficiency of the small lines is due to heat production by brown fat. These results are consistent with available observations on natural populations, that selection for temperature adaptation probably has had some influence on body size in this species.

Brown adipose tissue of mice with gold thioglucose-induced obesity: effect of cold and diet.

Gold thioglucose (GTG)-obese mice have a larger than normal amount of brown adipose tissue (BAT) with ultrastructurally normal mitochondria. The tissue grows normally when the mice adapt to cafeteria feeding or to cold (8 degrees C). Acute exposure to cold causes a fairly normal thermogenic activation of BAT mitochondria of GTG-obese mice, both in dynamic and static phases of their obesity. However, chow-fed GTG-obese mice have BAT mitochondria that are in a low state of thermogenic activation, and these mice fail to respond to eating a cafeteria diet for 3 wk by a normal thermogenic activation of their BAT mitochondria. More prolonged cafeteria feeding for 11-13 wk, into the static phase of obesity, is associated with thermogenic activation of BAT mitochondria of GTG-obese mice. The capacity of GTG-obese mice to respond to noradrenaline (norepinephrine) by an increase in metabolic rate is greater than that of lean mice and is further enhanced by cold acclimation. It is concluded that BAT of the GTG-obese mouse is inherently functional, as is control of its thermogenic function and growth during cold exposure and cold acclimation. Dietary influences on BAT thermogenic function are, however, defective in the GTG-obese mouse at least during the dynamic phase of its obesity. The resulting failure of diet-induced thermogenesis would be expected to contribute to the known high metabolic efficiency of the GTG-obese mouse and, together with the hyperphagia, to the obesity induced by GTG.

Diminished respiratory responses of brown adipocytes isolated from BIO 14.6 dystrophic hamsters.

Catecholamine-induced thermogenesis is significantly diminished in BIO 14.6 cardiomyopathic hamsters as demonstrated by a reduced increase in oxygen consumption of these hamsters in response to administered isoproterenol. This decreased responsiveness is accompanied by a reduction in the amount of brown adipose tissue, a major nonshivering thermogenic effector. The present study demonstrates that the metabolic responses of individual brown fat cells are also altered in the dystrophic hamster. That is, 1 microM norepinephrine, the physiological mediator of nonshivering thermogenesis, evoked rates of oxygen consumption that were significantly lower in brown adipocytes isolated from the BIO 14.6 hamsters than in those from normal controls. Additionally, the dystrophic adipocytes exhibited: decreased maximal activity (per cell as well as per milligram protein) of citrate synthase; decreased cell size; and decreased amounts of protein per cell. These data indicate that the nonshivering thermogenic capacity of the intact BIO 14.6 hamsters reflects altered characteristics of the individual brown adipocytes themselves, as well as decreased amounts of the tissue.

Brown adipose tissue in genetically obese (fa/fa) rats: response to cold and diet.

Young genetically obese (fatty, fa/fa) rats (7-8 wk old) maintained on a chow diet at 28 degrees C have a relatively normal amount of brown adipose tissue (BAT) (normal protein content, normal noradrenaline content, normal or slightly reduced cytochrome oxidase content, 30% reduction in DNA content) with cells grossly hypertrophied by accumulation of lipid. The binding of purine nucleotides by BAT mitochondria is lower in fa/fa rats than in lean rats, suggesting a lesser thermogenic activation of this tissue. Acute exposure to cold (24 h at 4 degrees C) activates BAT thermogenesis (visible hyperemia, marked increase in mitochondrial binding of purine nucleotides, depletion of noradrenaline content) in fa/fa rats as in lean rats. In contrast, feeding a cafeteria diet to young fa/fa rats fails to activate BAT (no increase in mitochondrial binding of purine nucleotides) as it does in lean rats, and these rats accumulate more extra fat (increase in weight of gonadal white adipose tissue) than do cafeteria diet-fed lean rats. It is concluded that the young fa/fa rat has normal cold-induced nonshivering thermogenesis in BAT but defective diet-induced thermogenesis in BAT and that the consequent reduction in energy expenditure, coupled with hyperphagia, contributes to the development of its obesity. The most probable location for the defect is suggested to be associated with the hypothalamus.

Abnormal brown adipose tissue in hamsters with muscular dystrophy.

The size (wet weight, total protein, total cytochrome oxidase) of interscapular brown adipose tissue is reduced to about one-half of normal in the cardiomyopathic hamster (BIO 14.6). The mitochondria are normal in binding of purine nucleotides [guanosine 5'-diphosphate (GDP)] and in proportion of polypeptides in the region of 32,000, both indices of the thermogenic proton conductance pathway, and in specific activity of cytochrome oxidase. Brown adipose tissue of the cardiomyopathic hamster can grow during acclimation to 4 degrees C, but its size remains smaller than in cold-acclimated normal hamsters. Mitochondrial polypeptide composition is not altered by acclimation to cold, but a large increase in mitochondrial GDP binding occurs in both normal and cardiomyopathic hamsters. The reduced calorigenic response of cardiomyopathic hamsters to catecholamines (Horwitz, B.A., and G.E. Hanes, Proc. Soc. Exp. Biol. Med. 147: 393-395, 1974) may, at least in part, be explained by a reduction in the amount of brown adipose tissue, the major site of this response. A defect in control of growth of this tissue in the cardiomyopathic hamster is suggested.

Noradrenaline-induced calorigenesis in warm- and in cold-acclimated rats: the interrelation of dose of noradrenaline, its concentration in arterial plasma, and calorigenic response.

Barbital-sedated, warm-acclimated (WA) or cold-acclimated (CA) rats were infused intravenously with noradenaline (NA) at doses of 0, 2.5, 5.0, and 10 ng min−1 g−0.74 body weight during a period of 30 min. Concentration of NA in arterial plasma, O2 consumption. and rectal temperature were measured before, during, and after NA infusion. Upon infusion of NA, plasma NA increased rapidly to a plateau level which was directly related to the dose infused. However, for each dose, the level was much lower in CA than in WA rats. In both WA and CA rats the increase in O2 consumption above the preinfusion rate was linearly related to the increase in the concentration of plasma NA, but the increase in O2 consumption with each dose was greater in CA than in WA rats. Thus, the slope of the relation between increase in O2 consumption and increase in plasma NA was greater by 4.7 times in CA than in WA rats. Differences in calorigenic response to circulating NA are attributed to a greater amount of brown adipose tissue (BAT) and to a higher calorigenic capacity per gram of this tissue in CA that in WA rats. The molar concentrations of circulating NA which stimulated calorigenesis in the intact white rat are in the same range (from 10−9 to 10−7 M) as those reported by others to stimulate O2 consumption of isolated hamster brown adipocytes and of perifused rat BAT fragments. It is suggested that circulating levels of NA which are effective in stimulating calorigenesis in the intact animal approximate average synaptic concentrations of NA in calorigenic effectors during noradrenergic nerve stimulation resulting from cold exposure.

Melatonin stimulates growth of brown adipose tissue.

IN small mammals brown adipose tissue (BAT) is an important site of non-shivering heat production1,2. Its mass increases during cold adaptation together with the ability to produce heat (ref. 3 and G. H., unpublished), thus improving cold tolerance4. In the golden hamster, Hoffman et al.5 also found an increase of BAT weight following exposure to short photoperiods. The pineal hormone melatonin has been shown to affect photoperiodic responses (ref. 6, and K. H. and G. H., unpublished), and therefore an action of melatonin on development of BAT seemed likely. In this study, the effect of short photoperiods and of melatonin on the amount of BAT was investigated in the Djungarian hamster Phodopus sungorus. This species shows a marked annual cycle of testis size and activity, body weight, and coat colour when kept under natural light conditions7, and all of these functions can be influenced by manipulation of the photoperiod (ref. 6, and K. H. and G. H., unpublished). The species does not hibernate, but may show daily torpor in winter, while the gonads are regressed even at room temperature7.