α- and β-adrenergic control of thermogenin mRNA expression in brown adipose tissue

1986 ◽  
Vol 6 (7) ◽  
pp. 621-631 ◽  
Author(s):  
Anders Jacobsson ◽  
Jan Nedergaard ◽  
Barbara Cannon
Keyword(s):  
Adipose Tissue ◽  
Cold Stress ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Fold Increase ◽  
Intracellular Camp ◽  
Brown Adipose ◽  
Camp Levels

By the use of an earlier characterised cDNA clone, CIN-1, corresponding to a sequence of the mRNA coding for the brown-fat specific “uncoupling” protein, thermogenin, the amount of thermogenin mRNA found in the brown adipose tissue of mice was quantitatively investigated under different physiological and pharmacological conditions. It was found that a 4 hr cold stress led to a 7-fold increase in the amount of thermogenin mRNA; injection of norepinephrine had a significant but smaller effect. Most notably, isoprenaline (β-agonist) and phenylephrine (α-agonist) had in themselves no effect, but when injected together were able to increase the mRNA level synergistically. In 4 hr cold-stressed mice, norepinephrine, isoprenaline and cholera toxin could all further potentiate the effect of the cold stress itself on the mRNA level. Insulin and the glucocorticoid dexamethasone both had weak stimulatory effects on the mRNA level. It is concluded that an increase in intracellular cAMP levels is a necessary and perhaps sufficient stimulus for the increase in thermogenin gene expression. However, at least under in vivo conditions, this increase requires stimulation of both α- and β-adrenergic pathways.

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.

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.

The influence of starvation and natural refeeding on the rate of triacylglycerol/fatty acid substrate cycling in brown adipose tissue and different white adipose sites of the rat in vivo. The role of insulin and the sympathetic nervous system

1988 ◽  
Vol 8 (2) ◽  
pp. 147-153 ◽  
Author(s):  
Stewart W. Mercer ◽  
Dermot H. Williamson
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fold Increase ◽  
Chow Diet ◽  
Fatty Acid Substrate ◽  
Brown Adipose ◽  
Acute Increase ◽  
Acid Substrate

Triacylglycerol/fatty acid substrate cycling was measured in vivo in brown adipose tissue (BAT) and white adipose tissue (WAT) of fed, starved and refed rats. Starvation (24 h) significantly decreased the rate of cycling in BAT, and refeeding chow diet led to a rapid, 6-fold increase in cycling. Cycling rate in WAT was much lower than in BAT, and was not influenced by fasting or refeeding. Similar rates of cycling were found in epididymal, mesenteric, subcutaneous, and scapular WAT depots. Sympathetic denervation of interscapular BAT abolished the response of the tissue to refeeding, as did acute suppression of insulin secretion. Similarly, rats fasted for 3 days showed no acute increase in the activity of the cycle following refeeding.

scholarly journals Glucose utilization by interscapular brown adipose tissue in vivo during nutritional transitions in the rat

1991 ◽  
Vol 273 (1) ◽  
pp. 233-235 ◽  
Author(s):  
M J Holness ◽  
Y L Liu ◽  
J S Beech ◽  
M C Sugden
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Utilization ◽  
Fold Increase ◽  
Interscapular Brown Adipose Tissue ◽  
Overall Response ◽  
Brown Adipose ◽  
Control Post

Glucose utilization indices (GUI) of interscapular brown adipose tissue (IBAT) declined by 84% after 48 h starvation. Two-thirds of the overall response was observed within 6 h, correlating with decreased insulin concentrations. Re-feeding 48 h-starved rats restored insulin concentrations and evoked a rapid 15-fold increase in IBAT GUI. GUI values after re-feeding were markedly higher than those observed at equivalent insulin concentrations in control post-absorptive rats.

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 Effects of burn injury, cold stress and cutaneous wound injury on the morphology and energy metabolism of murine brown adipose tissue (BAT) in vivo

Life Sciences ◽  
2011 ◽  
Vol 89 (3-4) ◽  
pp. 78-85 ◽  
Author(s):  
Edward A. Carter ◽  
Ali A. Bonab ◽  
Victoria Hamrahi ◽  
Justin Pitman ◽  
Daniel Winter ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Cold Stress ◽  
Brown Adipose Tissue ◽  
Burn Injury ◽  
Cutaneous Wound ◽  
Brown Adipose

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 Postnatal recruitment of brown adipose tissue is induced by the cold stress experienced by the pups. An analysis of mRNA levels for thermogenin and lipoprotein lipase

1989 ◽  
Vol 259 (2) ◽  
pp. 341-346 ◽  
Author(s):  
M J Obregón ◽  
A Jacobsson ◽  
T Kirchgessner ◽  
M C Schotz ◽  
B Cannon ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cold Stress ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Rat Pups ◽  
Brown Adipose ◽  
Actin Mrna ◽  
Clear Increase

In order to investigate the postnatal recruitment process, gene expression in the brown adipose tissue of rat pups was followed during the first 20 h of life. In normal pups, the level of mRNA coding for the uncoupling protein thermogenin increased markedly but gradually within the first 24 h. Lipoprotein lipase and actin mRNA levels were relatively low and remained constant. In pups exposed to thermoneutral temperature (35 degrees C) for the first 12 h after birth, no increase in thermogenin mRNA or lipoprotein lipase mRNA was observed, whereas in pups exposed to 28 degrees C a clear increase in both thermogenin and lipoprotein lipase mRNA levels was found. Actin mRNA levels were not affected by the environmental temperature under these circumstances. It was concluded that the postnatal recruitment in brown adipose tissue is a consequence of the cold stress experienced by the newborn pups. Thus, postnatal recruitment is not ontogenically predetermined.

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.

scholarly journals Mitochondrial matrix protein Letmd1 maintains thermogenic capacity of brown adipose tissue

2021 ◽  
Author(s):  
Anna Park ◽  
Kwang-eun Kim ◽  
Isaac Park ◽  
Dae-Soo Kim ◽  
Jaehoon Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cold Stress ◽  
Brown Adipose Tissue ◽  
Matrix Protein ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Mitochondrial Matrix ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

Abstract Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (Ucp1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here we identify LETM1 domain-containing protein 1 (Letmd1) is a BAT-enriched, cold-induced protein that is required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that Letmd1 is a mitochondrial matrix protein. Letmd1 knockout mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. Taken together, we identify that the BAT-enriched mitochondrial matrix protein Letmd1 is required for cold-stimulated respiration and thermogenic function of BAT.

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