Evidence against a Mediatory Role of Brown Adipose Tissue in the Calorigenic Response of Cold-Acclimated Rats to Noradrenaline

1974 ◽  
Vol 52 (6) ◽  
pp. 1051-1062 ◽  
Author(s):  
David O. Foster

The calorigenic response to infused noradrenaline (NA) of barbital-anesthetized, cold-acclimated, adult, gnotobiotic, albino rats tested 1 h after removal of interscapular brown adipose tissue (I.B.A.T.) was 14% lower than before surgery and 15% lower than the response of either sham-operated or non-operated rats; but 4 days later, the response of rats without I.B.A.T. was not significantly different from that of the controls. In unanesthetized rats, response to NA was also unaffected by interruption of blood flow to I.B.A.T. 1–3 days before the measurements. Since these results do not conform with previous findings of 30–60% reductions in response to NA following removal of I.B.A.T. or interference with the tissue's vascular connections, they contradict the current hypothesis that the B.A.T. of cold-acclimated rodents has a unique role as a mediator of calorigenesis in other tissues.A supplementary feature of the study was the discovery of apparent thermolability in the process by which cold-acclimated rats respond calorigenically to NA. If, during infusion of NA, colonic temperature exceeded about 41.5 °C, an apparently critical degree of hyperthermia response to the hormone during a subsequent infusion was reduced. This reduction was linearly related to the previous maximum colonic temperature over the range 41.6–42.4 °C and amounted to approximately 70% at 42.4 °C. These results indicate the necessity for monitoring the body temperatures of animals during infusion of NA, particularly in experiments in which two or more tests of response to NA are done on the same animal. Since such temperature measurements were not reported in those studies that have suggested a mediatory role of B.A.T. in calorigenesis in rodents, it is not possible to resolve the discrepancies on this basis.

1972 ◽  
Vol 50 (2) ◽  
pp. 168-170 ◽  
Author(s):  
J. S. Hayward ◽  
P. F. Davies

The increased rate of oxygen consumption by cold-acclimated, adult mice after subcutaneous injection of noradrenaline has been measured for intact individuals and for those with the arterial supply to their interscapular brown adipose tissue ligated. An immediate reduction of 40% of this calorigenic response was noted in mice thus operated. Dissection of the total brown fat of the body indicated that the interscapular deposits comprise 43% by weight of the total brown adipose tissue, which in turn forms only 1% of the body weight. Since a 40% reduction in calorigenic response to noradrenaline cannot be ascribed to the loss of an amount of brown fat constituting less than 0.5%) of the body weight, the results support the hypothesis that brown fat can mediate calorigenic responses of other tissues.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 142-OR
Author(s):  
MASAJI SAKAGUCHI ◽  
SHOTA OKAGAWA ◽  
SAYAKA KITANO ◽  
TATSUYA KONDO ◽  
EIICHI ARAKI

1983 ◽  
Vol 245 (6) ◽  
pp. E582-E586 ◽  
Author(s):  
M. Hayashi ◽  
T. Nagasaka

Fasting-induced changes in thermogenic responses to norepinephrine (NE, 4.0 micrograms X kg-1 X min-1 iv) were studied in anesthetized rats previously cold acclimated. The rats were divided into five groups at the end of 30–40 days of cold acclimation (5 degrees C). The five groups were kept for 5 days at 25 degrees C and fed (intact fed), fasted (intact fasted), fasted with daily treatment with thyroxine (T4, 2 micrograms/kg sc), thyroidectomized and fed, or thyroidectomized and fasted. In the intact fasted group, in which the weight of brown adipose tissue decreased, NE-induced increases in oxygen consumption, colonic temperature (T col), and temperature of the interscapular brown adipose tissue (TBAT) were markedly suppressed. The two thyroidectomized groups also showed a reduction in thermogenic response. In these three groups, TBAT was lower than Tcol throughout NE infusion. In the T4-treated fasted group, fasting-induced suppression of thermogenic response to NE was largely prevented. In the intact fed and the T4-treated fasted groups, TBAT attained higher values than Tcol during NE infusion. Plasma levels of thyroid hormones were significantly lower in the intact fasted group than in the intact fed or the T4-treated fasted group. These results suggest that fasting-induced suppression of the thermogenic response to NE is largely due to the reduced thermogenic response of brown adipose tissue to NE. The lowering of the levels of the thyroid hormones induced by fasting may be one of a number of causes of the reduction in the thermogenic response of brown adipose tissue.


2003 ◽  
Vol 228 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Yuesheng Li ◽  
Joanne R. Knapp ◽  
John J. Kopchick

Growth hormone (GH) acts on adipose tissue by accelerating fat expenditure, preventing triglyceride accumulation, and facilitating lipid mobilization. To investigate whether GH is involved in the development and metabolism of interscapular brown adipose tissue (BAT), a site of nonshivering thermogenesis, we employed three lines of transgenic mice. Two of the lines are dwarf due to expression of a GH antagonist (GHA) or disruption of the GH receptor/binding-protein gene. A third mouse line is giant due to overexpression of a bovine GH (bGH) transgene. We have found that the body weights of those animals are proportional to their body lengths at 10 weeks of age. However, GHA dwarf mice tend to catch up with the nontransgenic (NT) littermates in body weight but not in body length at 52 weeks of age. The increase of body mass index (BMI) for GHA mice accelerates rapidly relative to controls as a function of age. We have also observed that BAT in both dwarf mouse lines but not in giant mice is enlarged in contrast to nontransgenic littermates. This enlargement occurs as a function of age. Northern analysis suggests that BAT can be a GH-responsive tissue because GHR/BP mRNAs were found there. Finally, the level of uncoupling protein-1 (UCP1) RNA was found to be higher in dwarf mice and lower in giant animals relative to controls, suggesting that GH-mediated signaling may negatively regulate UCP1 gene expression in BAT.


2021 ◽  
pp. 10-18
Author(s):  
Irina Chernukha ◽  
Liliya Fedulova ◽  
Elena Kotenkova

Introduction. Traditionally, mammalian adipose tissue is divided into white (white adipose tissue – WAT) and brown (brown adipose tissue – BAT). While the functions of WAT are well known as the triglyceride depot, the role of BAT in mammalian physiology has been under close investigation. The first description of the role of BAT in maintaining thermogenesis dates back to 1961. This article offers a review of structural and functional specificity of white, beige and brown adipose tissue. Results and discussion. The differences and descriptions of adipocytes and their impact on the maintenance of the main functions of the mammalian body are described in this manuscript. In particular, thermogenesis, stress response, obesity, type II diabetes. In addition to WAT and BAT, an intermediate form was also detected in the body – beige fat (BeAT or Brite). The opposite opinions regarding the presence of three types of adipose tissue in the human and animal bodies are presented. Studies on the identification of uncoupling proteins 1 and 3 and their role in the transformation of white fat into beige/brown are considered. Basically, the data on the factors of endogenous and exogenous nature on their formation are given on the example of the human body. Conclusion. With an abundance of publications on the keywords: “white, brown fat”, these studies, in the overwhelming majority, are devoted to the role of these fats in the formation of human thermogenesis, the assessment of the impact on obesity. Pigs have also been suggested to lack functional BAT, which is a major cause of neonatal death in the swine industry, therefore the focus on investigating role of different types of adipose tissue in pigs seems very promising in order to understand whether there is a compensating mechanism of thermogenesis.


1977 ◽  
Vol 55 (3) ◽  
pp. 695-699 ◽  
Author(s):  
W. A. Behrens ◽  
Florent Depocas

Dopamine-β-hydroxylase (DBH) (EC 1.14.17.1) activity is present in the interscapular brown adipose tissue (IBAT) as early as 2 days of age in the white rat. The specific and the total activities of this enzyme, as well as those of cytochrome oxidase (COX) (EC 1.9.3.1) in IBAT increase up to at least 20 days of age. Daily administration of 6-hydroxydopamine (6-OHDA) between the second and the twelfth day after birth does not significantly alter IBAT weight gain relative to untreated controls, but the increase in protein content with age is reduced to about half the normal value at the end of the treatment. The treatment with 6-OHDA also results in a drastic lowering of DBH specific and total activities, and a much smaller rate of increase of COX specific and total activities with age in IBAT compared with controls. These results provide additional evidence for a previously proposed role of sympathetic nervous system activity in the development of the thermogenic potential of IBAT in the newborn rat.


1991 ◽  
Vol 69 (12) ◽  
pp. 1896-1900 ◽  
Author(s):  
Anette Meywirth ◽  
Uwe Redlin ◽  
Stephan Steinlechner ◽  
Gerhard Heldmaier ◽  
Russel J. Reiter

The importance of the sympathetic innervation in the regulation of 5′-deiodinase activity in the interscapular brown adipose tissue (BAT) of the Djungarian hamster was studied. Interscapular BAT of Djungarian hamsters was either unilaterally or bilaterally denervated, and thereafter the animals were maintained at thermoneutral temperature or exposed to 0 °C for 24 h. Denervation reduced the norepinephrine content to 2–10% of the level in the control groups. Unilateral denervation was as effective as bilateral denervation in depressing the norepinephrine content of the interscapular BAT. Cold exposure for 24 h resulted in a pronounced 5′-deiodinase activation. Denervation reduced, but did not completely prevent, the cold-induced increase in 5′-deiodinase activity. The basal level of 5′-deiodinase activity at thermoneutral temperature was not reduced by denervation. We conclude that cold-induced activation of BAT 5′-deiodinase primarily depends on the intact sympathetic innervation.Key words: nonshivering thermogenesis, brown fat, 5′-deiodinase, Phodopus sungorus.


1998 ◽  
Vol 275 (1) ◽  
pp. R92-R98 ◽  
Author(s):  
Akiko Kobayashi ◽  
Toshimasa Osaka ◽  
Yoshio Namba ◽  
Shuji Inoue ◽  
Tai Hee Lee ◽  
...  

Subcutaneous administration of capsaicin (5 mg/kg) immediately increased the temperature of the tail skin (Tsk) for 2 h in urethan-anesthetized rats, suggesting an increase in heat loss. O2 consumption, an index of heat production, also immediately increased after the capsaicin injection, and this increase lasted for >10 h. Colonic temperature (Tco) decreased within 1 h after the injection, and this decrease was followed by a long-lasting hyperthermic period. Adrenal demedullation largely attenuated the capsaicin-induced increase in O2consumption, and sympathetic denervation of the interscapular brown adipose tissue partly attenuated the increase in O2 consumption. However, capsaicin-induced heat loss was normal in these rats. In rats with cutaneous vasodilation maximized by warming and administration of hexamethonium, capsaicin did not further increase Tsk but normally induced heat production, and Tco gradually rose without a hypothermic period. Thus capsaicin simultaneously increased heat loss and heat production, and inhibition of one response did not affect the other. These findings suggest that capsaicin simultaneously activates independent networks for heat loss and heat production.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Arvand Asghari ◽  
Linh Bui ◽  
Robert Stephen ◽  
Michihisa Umetani

Abstract 27-Hydroxycholesterol (27HC) is the most abundant oxysterol in circulation and metabolized by a P450 enzyme CYP7B1. Its levels closely correspond to those of cholesterol in the body. In addition, previously it was found that 27HC is an endogenous selective estrogen receptor modulator (SERM), which links cholesterol metabolism to estrogen receptor actions (1). Brown adipose tissue (BAT) is the primary source of energy expenditure and energy homeostasis, as well as body temperature maintenance. While previously it was believed that BAT activity is limited to neonates and young children, it is now recognized that BAT is also active in adult humans and its function is impaired by metabolic diseases such as obesity. BAT is also a secretory organ and produces brown adipokines, although the exact function of BAT and adipokines from this tissue in obesity has not been completely understood. Recently, it was reported that 27HC plays an important role in obesity and augments body weight gain in response to a high fat, high cholesterol (HFHC) diet by increasing pre-adipocyte population in the white adipose tissue. 27HC mimics the effects by HFHC diet-feeding on white adipose tissue, such as promoting the inflammation and macrophage infiltration (2). In this study, we explored the effect of 27HC on BAT morphology and function. First, we compared the morphology of BAT from wild-type mice and Cyp7b1-/- mice that have elevated levels of 27HC using H&E staining. Interestingly, brown adipocytes from Cyp7b1-/- mice were larger in cell size than those from wild-type mice, and the cells were mostly unilocular compared to the multilocular cells from wild-type mice, indicating the transition toward a “whitening” phenotype. Next, We treated mice fed a normal chow or a HFHC diet with 27HC or vehicle control for 8 weeks to examine the direct effect by 27HC on BAT. Similar to the phenotype in Cyp7b1-/-mice, 27HC increased the “whitening” of BAT regardless of the diet. We also determined the gene expression of brown adipocyte markers such as UCP1, PGC1a, and DIO2, and found that 27HC significantly decreased the expression of the BAT markers regardless of the diet, confirming the “whitening” observed in the morphology. Moreover, the energy expenditure in mice treated with 27HC was decreased compared to the vehicle control on a HFHC diet, suggesting that 27HC also alters BAT function. These results show that 27HC causes the whitening of BAT, and shed light on the important role of 27HC in brown adipose tissue function. Future experiments will be warranted toward further understanding of the role of 27HC in BAT function. Reference:(1) Umetani, Michihisa, et al. Nature medicine 13.10 (2007): 1185. (2) Asghari, Arvand, et al. Endocrinology 160.10 (2019): 2485-2494.


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