Brown Adipose Tissue: Function and Physiological Significance

2004 ◽  
Vol 84 (1) ◽  
pp. 277-359 ◽  
Author(s):  
BARBARA CANNON ◽  
JAN NEDERGAARD

Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogen-esis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.

2018 ◽  
Vol 238 (1) ◽  
pp. R53-R62 ◽  
Author(s):  
Michael E Symonds ◽  
Peter Aldiss ◽  
Neele Dellschaft ◽  
James Law ◽  
Hernan P Fainberg ◽  
...  

Although brown adipose tissue (BAT) is one of the smallest organs in the body, it has the potential to have a substantial impact on both heat production as well as fat and carbohydrate metabolism. This is most apparent at birth, which is characterised with the rapid appearance and activation of the BAT specific mitochondrial uncoupling protein (UCP)1 in many large mammals. The amount of brown fat then gradually declines with age, an adaptation that can be modulated by the thermal environment. Given the increased incidence of maternal obesity and its potential transmission to the mother’s offspring, increasing BAT activity in the mother could be one mechanism to prevent this cycle. To date, however, all rodent studies investigating maternal obesity have been conducted at standard laboratory temperature (21°C), which represents an appreciable cold challenge. This could also explain why offspring weight is rarely increased, suggesting that future studies would benefit from being conducted at thermoneutrality (~28°C). It is also becoming apparent that each fat depot has a unique transcriptome and show different developmental pattern, which is not readily apparent macroscopically. These differences could contribute to the retention of UCP1 within the supraclavicular fat depot, the most active depot in adult humans, increasing heat production following a meal. Despite the rapid increase in publications on BAT over the past decade, the extent to which modifications in diet and/or environment can be utilised to promote its activity in the mother and/or her offspring remains to be established.


2011 ◽  
Vol 32 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Leopoldo De Meis ◽  
Luisa A. Ketzer ◽  
Juliana Camacho-Pereira ◽  
Antonio Galina

The UCP1 [first UCP (uncoupling protein)] that is found in the mitochondria of brown adipocytes [BAT (brown adipose tissue)] regulates the heat production, a process linked to non-shivering thermogenesis. The activity of UCP1 is modulated by GDP and fatty acids. In this report, we demonstrate that respiration and heat released by BAT mitochondria vary depending on the respiratory substrate utilized and the coupling state of the mitochondria. It has already been established that, in the presence of pyruvate/malate, BAT mitochondria are coupled by faf-BSA (fatty-acid-free BSA) and GDP, leading to an increase in ATP synthesis and mitochondrial membrane potential along with simultaneous decreases in both the rates of respiration and heat production. Oleate restores the uncoupled state, inhibiting ATP synthesis and increasing the rates of both respiration and heat production. We now show that in the presence of succinate: (i) the rates of uncoupled mitochondria respiration and heat production are five times slower than in the presence of pyruvate/malate; (ii) faf-BSA and GDP accelerate heat and respiration as a result and, in coupled mitochondria, these two rates are accelerated compared with pyruvate/malate; (iii) in spite of the differences in respiration and heat production noted with the two substrates, the membrane potential and the ATP synthesized were the same; and (iv) oleate promoted a decrease in heat production and respiration in coupled mitochondria, an effect different from that observed using pyruvate/malate. These effects are not related to the production of ROS (reactive oxygen species). We suggest that succinate could stimulate a new route to heat production in BAT mitochondria.


2020 ◽  
Author(s):  
Christopher L. Riley ◽  
Edward M. Mills

AbstractMitochondrial uncoupling protein 3 (UCP3) plays a complementary role in uncoupling protein 1 (UCP1)-dependent uncoupling in mammalian thermogenesis. Using mouse strains that lack UCP1 or UCP3, plus a UCP1/UCP3 double knockout, we have previously demonstrated that UCP3 is necessary for sustained heat production. However, how and where UCP3 is essential for heat production remains unknown. Here we use brown adipocyte mitochondria from mice lacking UCP1, UCP3, or UCP1 plus UCP3 (double knockout) we found that in the absence of UCP1, UCP3 does not act as a free fatty acid-inducible uncoupling protein; however, UCP3 is necessary for maximal GDP-sensitive respiration. We additionally confirm that the loss of UCP1 is a dominant regulator of mitochondrial respiratory chain activity, assembly, and composition in brown adipose tissue. Our data suggest without UCP1, brown adipose tissue is not a significant source of heat production, and that UCP3-dependent heat generation serves a regulatory function outside of adipose tissues. Together these findings suggest that in brown adipose tissue, UCP3’s thermogenic function is independent of its role as a bona fide uncoupling protein.


Author(s):  
Martin Jastroch ◽  
Elias T. Polymeropoulos ◽  
Michael J. Gaudry

AbstractThe thermogenic mechanisms supporting endothermy are still not fully understood in all major mammalian subgroups. In placental mammals, brown adipose tissue currently represents the most accepted source of adaptive non-shivering thermogenesis. Its mitochondrial protein UCP1 (uncoupling protein 1) catalyzes heat production, but the conservation of this mechanism is unclear in non-placental mammals and lost in some placentals. Here, we review the evidence for and against adaptive non-shivering thermogenesis in marsupials, which diverged from placentals about 120–160 million years ago. We critically discuss potential mechanisms that may be involved in the heat-generating process among marsupials.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2499
Author(s):  
Annett Hoffmann ◽  
Thomas Ebert ◽  
Mohammed K. Hankir ◽  
Gesine Flehmig ◽  
Nora Klöting ◽  
...  

Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the dysregulation of several key adipokines, including leptin. Treatment with leptin or its analogues is therefore sufficient to reverse some of the metabolic symptoms of LD in patients and in mouse models through distinct mechanisms. Brown adipose tissue (BAT) thermogenesis has emerged as an important regulator of systemic metabolism in rodents and in humans, but it is poorly understood how leptin impacts BAT in LD. Here, we show in transgenic C57Bl/6 mice overexpressing sterol regulatory element-binding protein 1c in adipose tissue (Tg (aP2-nSREBP1c)), an established model of congenital LD, that daily subcutaneous administration of 3 mg/kg leptin for 6 to 8 weeks increases body temperature without affecting food intake or body weight. This is associated with increased protein expression of the thermogenic molecule uncoupling protein 1 (UCP1) and the sympathetic nerve marker tyrosine hydroxylase (TH) in BAT. These findings suggest that leptin treatment in LD stimulates BAT thermogenesis through sympathetic nerves, which might contribute to some of its metabolic benefits by providing a healthy reservoir for excess circulating nutrients.


1994 ◽  
Vol 269 (10) ◽  
pp. 7435-7438
Author(s):  
D.L. Murdza-Inglis ◽  
M. Modriansky ◽  
H.V. Patel ◽  
G. Woldegiorgis ◽  
K.B. Freeman ◽  
...  

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Haiying Zhou ◽  
Bo Wan ◽  
Ivan Grubisic ◽  
Tommy Kaplan ◽  
Robert Tjian

Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (UCP1). Previously, we reported that the TATA-binding protein associated factor 7L (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation. In this study, we show that TAF7L also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing TFIID complexes associate with PPARγ to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that the presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification.


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