Increased thermogenic capacity of brown adipose tissue under low temperature and its contribution to arousal from hibernation in Syrian hamsters

2012 ◽  
Vol 302 (1) ◽  
pp. R118-R125 ◽  
Author(s):  
Naoya Kitao ◽  
Masaaki Hashimoto
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Brown Adipose Tissue ◽  
Time Course ◽  
Uncoupling Protein ◽  
Physiological Role ◽  
Adrenergic System ◽  
Syrian Hamsters ◽  
Brown Adipose

Brown adipose tissue (BAT) is thought to play a significant physiological role during arousal when body temperature rises from the extremely low body temperature that occurs during hibernation. The dominant pathway of BAT thermogenesis occurs through the β3-adrenergic receptor. In this study, we investigated the role of the β3-adrenergic system in BAT thermogenesis during arousal from hibernation both in vitro and in vivo. Syrian hamsters in the hibernation group contained BAT that was significantly greater in overall mass, total protein, and thermogenic uncoupling protein-1 than BAT from the warm-acclimated group. Although the ability of the β3-agonist CL316,243 to induce BAT thermogenesis at 36°C was no different between the hibernation and warm-acclimated groups, its maximum ratio over the basal value at 12°C in the hibernation group was significantly larger than that in the warm-acclimated group. Forskolin stimulation at 12°C produced equivalent BAT responses in these two groups. In vivo thermogenesis was assessed with the arousal time determined by the time course of BAT temperature or heart rate. Stimulation of BAT by CL316,243 significantly shortened the time of arousal from hibernation compared with that induced by vehicle alone, and it also induced arousal in deep hibernating animals. The β3-antagonist SR59230A inhibited arousal from hibernation either in part or completely. These results suggest that BAT in hibernating animals has potent thermogenic activity with a highly effective β3-receptor mechanism at lower temperatures.

scholarly journals TAF7L modulates brown adipose tissue formation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Haiying Zhou ◽  
Bo Wan ◽  
Ivan Grubisic ◽  
Tommy Kaplan ◽  
Robert Tjian
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Core Promoter ◽  
Uncoupling Protein ◽  
Dna Looping ◽  
Chromatin Interactions ◽  
Brown Adipose ◽  
Important Regulator

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.

Selective loss of uncoupling protein mRNA in brown adipose tissue on deacclimation of cold-acclimated mice

1987 ◽  
Vol 65 (11) ◽  
pp. 955-959 ◽  
Author(s):  
Hasmukh V. Patel ◽  
Karl B. Freeman ◽  
Michel Desautels
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome C Oxidase ◽  
Time Course ◽  
Uncoupling Protein ◽  
Relative Proportion ◽  
Cdna Probe ◽  
Mitochondrial Content ◽  
Brown Adipose ◽  
Uncoupling Protein Mrna

The time course of changes in the level of uncoupling protein mRNA when cold-acclimated mice were returned to a thermoneutral environment (33 °C) was examined using a cDNA probe. Upon deacclimation, there was a marked loss of uncoupling protein mRNA within 24 h, which precedes the loss of uncoupling protein from mitochondria. This loss of uncoupling protein mRNA was selective, since there was no change in the relative proportion of cytochrome c oxidase subunit IV mRNA or poly(A)+ RNA in total RNA. The results suggest that the decrease in the mitochondrial content of uncoupling protein during deacclimation is likely the result of turnover of existing protein, with very little replacement due to a lower level of its mRNA.

scholarly journals Changes in uncoupling protein and GLUT4 glucose transporter expressions in interscapular brown adipose tissue of diabetic rats: relative roles of hyperglycaemia and hypoinsulinaemia

1993 ◽  
Vol 291 (1) ◽  
pp. 109-113 ◽  
Author(s):  
R Burcelin ◽  
J Kande ◽  
D Ricquier ◽  
J Girard
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Time Course ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Diabetic Rats ◽  
Plasma Insulin Concentration ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

We have studied the time course and relative effects of hypoinsulinaemia and hyperglycaemia on concentrations of uncoupling protein (UCP) and glucose transporter (GLUT4) and their mRNAs in brown adipose tissue (BAT) during the early phase of diabetes induced by streptozotocin. Two days after intravenous injection of streptozotocin, plasma insulin concentration was at its lowest and glycaemia was higher than 22 mmol/l. After 3 days, a 60% decrease in BAT UCP mRNA concentration and a 36% decrease in UCP was observed. Concomitantly, there was an 80% decrease in GLUT4 mRNA and a 44% decrease in GLUT4 levels. When hyperglycaemia was prevented by infusing phlorizin into diabetic rats, BAT UCP mRNA and protein levels were further decreased (respectively 90% and 60% lower than in control rats). In contrast, the marked decreases in GLUT4 mRNA and protein concentrations in BAT were similar in hyperglycaemic and normoglycaemic diabetic rats. Infusion of physiological amounts of insulin restored normoglycaemia in diabetic rats, and BAT UCP and GLUT4 mRNA and protein concentrations were maintained at the level of control rats. When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease. This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT. Hyperglycaemia partially prevents the rapid decrease in concentration of UCP and its mRNA observed in insulinopenic diabetes whereas it did not affect the decrease in GLUT4 mRNA and protein concentration. It is suggested that UCP is produced by a glucose-dependent gene.

scholarly journals Mitochondrial uncoupling protein may participate in futile cycling of pyruvate and other monocarboxylates

1998 ◽  
Vol 275 (2) ◽  
pp. C496-C504 ◽  
Author(s):  
Petr Jezek ◽  
Jirí Borecky
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Specific Inhibitor ◽  
Physiological Role ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose ◽  
Futile Cycling

The physiological role of monocarboxylate transport in brown adipose tissue mitochondria has been reevaluated. We studied pyruvate, α-ketoisovalerate, α-ketoisocaproate, and phenylpyruvate uniport via the uncoupling protein (UCP1) as a GDP-sensitive swelling in K+ salts induced by valinomycin or by monensin and carbonyl cyanide- p-(trifluoromethoxy)phenylhydrazone in Na+ salts. We have demonstrated that this uniport is inhibited by fatty acids. GDP inhibition in K+ salts was not abolished by an uncoupler, indicating a negligible monocarboxylic acid penetration via the lipid bilayer. In contrast, the electroneutral pyruvate uptake (swelling in ammonium pyruvate or potassium pyruvate induced by change in pH) mediated by the pyruvate carrier was inhibited by its specific inhibitor α-cyano-4-hydroxycinnamate but not by fatty acids. Moreover, α-cyano-4-hydroxycinnamate enhanced the energization of brown adipose tissue mitochondria, which was monitored fluorometrically by 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide and safranin O. Consequently, we suggest that UCP1 might participate in futile cycling of unipolar ketocarboxylates under certain physiological conditions while expelling these anions from the matrix. The cycle is completed on their return via the pyruvate carrier in an H+ symport mode.

scholarly journals Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-13C]Pyruvate MRI in Mice

2018 ◽  
Vol 19 (9) ◽  
pp. 2597 ◽  
Author(s):  
Mette Riis-Vestergaard ◽  
Peter Breining ◽  
Steen Pedersen ◽  
Christoffer Laustsen ◽  
Hans Stødkilde-Jørgensen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Fdg Pet ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Protein Levels ◽  
Positron Emission ◽  
Brown Adipose

The capacity to increase energy expenditure makes brown adipose tissue (BAT) a putative target for treatment of metabolic diseases such as obesity. Presently, investigation of BAT in vivo is mainly performed by fluoro-d-glucose positron emission tomography (FDG PET)/CT. However, non-radioactive methods that add information on, for example, substrate metabolism are warranted. Thus, the aim of this study was to evaluate the potential of hyperpolarized [1-13C]pyruvate Magnetic Resonance Imaging (HP-MRI) to determine BAT activity in mice following chronic cold exposure. Cold (6 °C) and thermo-neutral (30 °C) acclimated mice were scanned with HP-MRI for assessment of the interscapular BAT (iBAT) activity. Comparable mice were scanned with the conventional method FDG PET/MRI. Finally, iBAT was evaluated for gene expression and protein levels of the specific thermogenic marker, uncoupling protein 1 (UCP1). Cold exposure increased the thermogenic capacity 3–4 fold (p < 0.05) as measured by UCP1 gene and protein analysis. Furthermore, cold exposure as compared with thermo-neutrality increased iBAT pyruvate metabolism by 5.5-fold determined by HP-MRI which is in good agreement with the 5-fold increment in FDG uptake (p < 0.05) measured by FDG PET/MRI. iBAT activity is detectable in mice using HP-MRI in which potential changes in intracellular metabolism may add useful information to the conventional FDG PET studies. HP-MRI may also be a promising radiation-free tool for repetitive BAT studies in humans.

scholarly journals Pyruvate induces torpor in obese mice

2018 ◽  
Vol 115 (4) ◽  
pp. 810-815 ◽  
Author(s):  
Marion Soto ◽  
Lucie Orliaguet ◽  
Michelle L. Reyzer ◽  
M. Lisa Manier ◽  
Richard M. Caprioli ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Metabolic Rate ◽  
Brown Adipose Tissue ◽  
Mass Spectroscopy ◽  
Uncoupling Protein ◽  
Obese Mice ◽  
Uncoupling Protein 1 ◽  
Metabolic Intermediate ◽  
Brown Adipose

Mice subjected to cold or caloric deprivation can reduce body temperature and metabolic rate and enter a state of torpor. Here we show that administration of pyruvate, an energy-rich metabolic intermediate, can induce torpor in mice with diet-induced or genetic obesity. This is associated with marked hypothermia, decreased activity, and decreased metabolic rate. The drop in body temperature correlates with the degree of obesity and is blunted by housing mice at thermoneutrality. Induction of torpor by pyruvate in obese mice relies on adenosine signaling and is accompanied by changes in brain levels of hexose bisphosphate and GABA as detected by mass spectroscopy-based imaging. Pyruvate does not induce torpor in lean mice but results in the activation of brown adipose tissue (BAT) with an increase in the level of uncoupling protein-1 (UCP1). Denervation of BAT in lean mice blocks this increase in UCP1 and allows the pyruvate-induced torpor phenotype. Thus, pyruvate administration induces torpor in obese mice by pathways involving adenosine and GABA signaling and a failure of normal activation of BAT.

Brown adipose tissue development in the ovine foetus during the final month of gestation

1992 ◽  
Vol 15 ◽  
pp. 174-175
Author(s):  
L. Clarke ◽  
S. van de Waal ◽  
M. A. Lomax ◽  
M. E. Symonds
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Brown Adipose ◽  
Adipose Tissue Development ◽  
Lamb Growth ◽  
Shivering Thermogenesis ◽  
Thermogenic Capacity

In the ovine foetus brown adipose tissue (BAT) is mainly found in the perirenal region and grows rapidly relative to body weight between 70 to 120 days of gestation (Alexander, 1978). After this stage only a small amount of BAT growth occurs in comparison with that of the whole foetus, and in the case of undernutrition may decline (Alexander, 1978). Maternal cold stress, induced by winter shearing twin-bearing pregnant ewes 8 weeks before parturition improves lamb birth weight and lamb growth rate independently of effects on maternal food intake (Symonds, Bryant and Lomax, 1986 and 1990). At the same time this can stimulate the in vivo capacity for non-shivering thermogenesis in newborn lambs (Stott and Slee, 1985). The following study extends these findings by investigating the extent to which changing the maternal metabolic environment influences BAT development over the final month of gestation.Thirty-two Bluefaced Leicester × Swaledale ewes were housed individually at ambient temperature (−6 to 19°C) 6 weeks prior to lambing and 2 weeks later 15 ewes were shorn. Ewes were offered daily a diet comprising 200 g barley concentrate and 1 kg chopped hay. Between 116 and 145 days of gestation and within 2 h of birth ewes were humanely slaughtered with an overdose of barbiturate and foetal or neonatal perirenal BAT sampled, born from shorn or unshorn ewes. The thermogenic capacity of BAT was assessed by guanosine-5′-diphosphate (GDP) binding to uncoupling protein in mitochondrial preparations (Cooper, Dascombe, Rothwell and Vale, 1989) and the amount of mitochondrial protein measured from cytochrome Coxidase activity.

Adrenergically stimulated blood flow in brown adipose tissue is not dependent on thermogenesis

2015 ◽  
Vol 308 (9) ◽  
pp. E822-E829 ◽  
Author(s):  
Gustavo Abreu-Vieira ◽  
Carolina E. Hagberg ◽  
Kirsty L. Spalding ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Temperature Acclimation ◽  
The Body ◽  
Doppler Imaging ◽  
Dependent Manner ◽  
Brown Adipose

Brown adipose tissue (BAT) thermogenesis relies on blood flow to be supplied with nutrients and oxygen and for the distribution of the generated heat to the rest of the body. Therefore, it is fundamental to understand the mechanisms by which blood flow is regulated and its relation to thermogenesis. Here, we present high-resolution laser-Doppler imaging (HR-LDR) as a novel method for noninvasive in vivo measurement of BAT blood flow in mice. Using HR-LDR, we found that norepinephrine stimulation increases BAT blood flow in a dose-dependent manner and that this response is profoundly modulated by environmental temperature acclimation. Surprisingly, we found that mice lacking uncoupling protein 1 (UCP1) have fully preserved BAT blood flow response to norepinephrine despite failing to perform thermogenesis. BAT blood flow was not directly correlated to systemic glycemia, but glucose injections could transiently increase tissue perfusion. Inguinal white adipose tissue, also known as a brite/beige adipose tissue, was also sensitive to cold acclimation and similarly increased blood flow in response to norepinephrine. In conclusion, using a novel noninvasive method to detect BAT perfusion, we demonstrate that adrenergically stimulated BAT blood flow is qualitatively and quantitatively fully independent of thermogenesis, and therefore, it is not a reliable parameter for the estimation of BAT activation and heat generation.

scholarly journals Sequential changes in the expression of mitochondrial protein mRNA during the development of brown adipose tissue in bovine and ovine species. Sudden occurrence of uncoupling protein mRNA during embryogenesis and its disappearance after birth

1989 ◽  
Vol 257 (3) ◽  
pp. 665-671 ◽  
Author(s):  
L Casteilla ◽  
O Champigny ◽  
F Bouillaud ◽  
J Robelin ◽  
D Ricquier
Keyword(s):  
Adipose Tissue ◽  
Cytochrome C ◽  
Brown Adipose Tissue ◽  
Cytochrome C Oxidase ◽  
Uncoupling Protein ◽  
Subcutaneous Tissue ◽  
Mitochondrial Protein ◽  
Sequence Of Events ◽  
Brown Adipose

Samples of adipose tissue were obtained from different sites in bovine and ovine foetuses and newborns. RNA was isolated and analysed using bovine cDNA and ovine genomic probe for uncoupling protein (UCP), cDNA for subunits III and IV of cytochrome c oxidase and cDNA for ADP/ATP carrier. UCP mRNA was characterized for the first time in foetal bovine and ovine adipose tissue. It appeared later than mRNA of cytochrome c oxidase subunit III, and increased dramatically at birth (10-fold). ADP/ATP carrier mRNA was expressed at a lower level but also increased 10-fold at birth. It was demonstrated that UCP mRNA reached its highest level at birth in all bovine adipose tissues studied, except subcutaneous tissue. It disappeared quickly afterwards, being no longer detectable two days after birth. Similar variations were observed in newborn lambs. ADP/ATP carrier mRNA showed the same pattern of expression as UCP mRNA; although it was still lightly expressed two days after birth, it disappeared soon afterwards. Only mRNAs for cytochrome c oxidase subunits III and IV remained at the same level during the first postnatal week. On the basis of these data and of observations reported in the literature a sequence of events for the development of brown adipose cells in vivo is proposed. Soon after birth the perirenal adipose tissue of ruminants, which still contains mitochondria of typical brown adipose tissue morphology and high levels of cytochrome c oxidase mRNA, lacks UCP mRNA. Can it still be considered as brown fat? Ruminant species appear to be attractive models to study both the differentiation of brown adipose tissue and its possible conversion to white fat in large animals.

Effect of date of mating and housing on lamb growth, adipose tissue deposition and plasma leptin concentrations

2002 ◽  
Vol 2002 ◽  
pp. 86-86
Author(s):  
S. Pearce ◽  
A. Mostyn ◽  
E. Genever ◽  
D.H. Keisler ◽  
R. Webb ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Birth Weight ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Physiological Role ◽  
Fetal Life ◽  
Brown Adipose ◽  
Adipose Tissue Development ◽  
Plasma Leptin ◽  
Sheep Fetus

In lambs, the rapid increase in heat production after birth is due to initiation of nonshivering thermogenesis in brown adipose tissue (BAT). This occurs in conjunction with an increase in amount and activity of BAT specific uncoupling protein 1 (UCP1) (Clarke et al. 1997). UCP1 abundance and activity is low in fetal life but, within twelve hours of birth, there is an increase in the thermogenic activity of BAT and mRNA for UCP1. This ontogeny of UCP1 mRNA in BAT is very similar that of leptin, which is first detectable in the sheep fetus at 90 days gestation in fetal adipose tissue, its expression then increases up to term at 147 days (Yuen et al 1999). Leptin is a hormone which is thought to play a physiological role is in energy balance, it is primarily produced by white adipose tissue although there is evidence for its production in both brown adipose tissue and the placenta. Lambs born in the autumn are known to be smaller than those born in the spring (McCoard et al. 1997). It is not known if moderate changes in date of mating can influence birth weight or adipose tissue development. The present study aimed to determine whether date of mating could influence lamb birth weight, the abundance of BAT, UCP1, plasma leptin.

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