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

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.

1992 ◽  
Vol 15 ◽  
pp. 174-175
Author(s):  
L. Clarke ◽  
S. van de Waal ◽  
M. A. Lomax ◽  
M. E. Symonds

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.


1987 ◽  
Vol 252 (5) ◽  
pp. R987-R993 ◽  
Author(s):  
I. Levin ◽  
P. Trayhurn

The effects of different food deprivation regimens on the thermogenic activity and capacity of brown adipose tissue in the golden hamster have been investigated. Thermogenesis in the tissue was assessed by measurements of tissue cytochrome-c oxidase activity, mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein. The thermogenic activity and capacity of brown adipose tissue were found to be markedly reduced in fasted or underweight hamsters. Measurements of cytochrome-c oxidase activity indicate that the reductions were caused exclusively by a loss in mitochondrial mass, uncoupling protein concentration and GDP binding to mitochondria remaining unchanged. The decrease in brown adipose tissue thermogenesis was associated with a reduction in the capacity for nonshivering thermogenesis in the whole animal. Hamsters recovered from weight losses without increasing their food intake, and the recovery was accompanied by a normalization in mitochondrial mass in brown adipose tissue. Mitochondrial mass was, however, restored only after 10 days of ad libitum refeeding. These results suggest that the reduction in energy expenditure in the fasted hamster could relate to a decrease in brown adipose tissue thermogenesis, in addition to the previously reported decreases in resting metabolic rate and locomotor activity. Reductions in thermogenesis may also represent a further mechanism by which energy stores recover in the golden hamster without postfast hyperphagia.


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.


1987 ◽  
Vol 65 (11) ◽  
pp. 955-959 ◽  
Author(s):  
Hasmukh V. Patel ◽  
Karl B. Freeman ◽  
Michel Desautels

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.


1985 ◽  
Vol 231 (3) ◽  
pp. 761-764 ◽  
Author(s):  
R Bazin ◽  
D Ricquier ◽  
F Dupuy ◽  
J Hoover-Plow ◽  
M Lavau

The thermogenic capacity of brown adipose tissue has been investigated in I-strain mice to determine whether this tissue could play a role in the lower efficiency of food utilization reported in this strain of mice. (1) As compared with C57BL mice (a control strain), interscapular-brown-adipose-tissue weight and lipid percentage were decreased by 40% and 13% respectively in I-strain mice. (2) Mitochondrial protein content and cytochrome c oxidase activity were similar in the two strains, but the number of mitochondrial GDP-binding sites and uncoupling-protein content were increased by 2-fold in I-strain mice. (3) Fatty acid synthetase and citrate-cleavage enzyme (units/mg of protein) were 3-fold higher in the brown adipose tissue of I-strain mice. These results indicate that I-strain mice possess a very active brown adipose tissue. This enhanced capacity of energy dissipation in brown adipose tissue could contribute to the decreased capacity of I-strain mice to store adipose tissue.


2012 ◽  
Vol 302 (1) ◽  
pp. R118-R125 ◽  
Author(s):  
Naoya Kitao ◽  
Masaaki Hashimoto

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.


2018 ◽  
Vol 19 (9) ◽  
pp. 2597 ◽  
Author(s):  
Mette Riis-Vestergaard ◽  
Peter Breining ◽  
Steen Pedersen ◽  
Christoffer Laustsen ◽  
Hans Stødkilde-Jørgensen ◽  
...  

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.


1990 ◽  
Vol 258 (2) ◽  
pp. R418-R424 ◽  
Author(s):  
A. Geloen ◽  
P. Trayhurn

The role of insulin in the regulation of the thermogenic activity and capacity (uncoupling protein content) of brown adipose tissue (BAT) has been investigated using mice made diabetic with streptozotocin and then subsequently infused with different doses of insulin. After 12 days of diabetes, the animals received either 0, 8, 16, or 32 units of insulin.kg body wt-1.day-1 delivered by osmotic minipumps implanted subcutaneously for 12 days. After 12 days of diabetes, body weight, interscapular BAT, and epididymal white adipose tissue weights were each reduced. In BAT, significant decreases (P less than 0.05) in the mitochondrial protein content (63%), cytochrome oxidase activity (79%), mitochondrial GDP binding (51%), and the specific mitochondrial concentration and total tissue content of uncoupling protein (71 and 89%, respectively) were obtained, indicating that the thermogenic activity and capacity of the tissue were reduced in diabetes. The infusion of insulin at a dose of 8 units.kg-1.day-1 normalized mitochondrial GDP binding and doubled the concentration of uncoupling protein. Body weight, epididymal white adipose tissue weight, and the mitochondrial protein content of BAT were restored with 16 units of insulin.kg-1.day-1. Higher doses of insulin did not further increase the specific mitochondrial concentration of uncoupling protein, but the mitochondrial content (and thereby the total uncoupling protein content) of BAT was increased and blood glucose normalized. There was a significant correlation between the dose of insulin replacement and several of the parameters measured in BAT: mitochondrial protein content (r = 0.68, P less than 0.001), cytochrome oxidase activity (r = 0.54, P less than 0.001), and total uncoupling protein content (r = 0.68, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


2015 ◽  
Vol 308 (9) ◽  
pp. E822-E829 ◽  
Author(s):  
Gustavo Abreu-Vieira ◽  
Carolina E. Hagberg ◽  
Kirsty L. Spalding ◽  
Barbara Cannon ◽  
Jan Nedergaard

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.


1997 ◽  
Vol 77 (6) ◽  
pp. 871-883 ◽  
Author(s):  
Lynne Clarke ◽  
Michael J. Bryant ◽  
Michael A. Lomax ◽  
Michael E. Symonds

AbstractWe examined the effect of maternal chronic cold exposure, induced by winter-shearing ewes 4 weeks before their predicted lambing date, on brown adipose tissue (BAT) and liver development in lambs. Fetuses were sampled from under-fed (60% of energy requirements for maintenance and pregnancy of an unshorn ewe) shorn or unshorn ewes at 126,140 and 145 d of gestation. Lambs were sampled from ewes within 2 h of birth. Throughout gestation fetal body, BAT and liver weights were similar in shorn and unshorn groups. The level of GDP binding to mitochondrial uncoupling protein remained low throughout gestation, but increased dramatically after birth. Lambs born to shorn ewes possesd more mitochondrial protein and exhibited a significantly higher total thermogenic activity in BAT. Type I iodothyronine 5 deiodinas(EC 3.8.1.4) activity in BAT peaked at birth, as did hepatic iodothyronine Sdeiodinase activity and was significantly greater in lambs born to under-fed shorn ewes, which exhibited a higher plasma triiodothyronine concentration. Chronic maternal adaptations to prolonged cold exposure appear to enable pregnant ewes to compensate for the negative effects of under-feeding on fetal growth and development


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