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 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.

Glucocorticoids and regulation of brown adipose tissue in humans – physiological and pathophysiological considerations

2017 ◽  
Vol 86 (3) ◽  
pp. 227
Author(s):  
Aleksander Rajczewski ◽  
Magdalena Gibas-Dorna
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
The Body ◽  
Adrenergic Stimulation ◽  
Therapeutic Goals ◽  
Bat Activity ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Differentiation And Proliferation

This review discusses the effects of glucocorticoids (GCs) on brown adipose tissue (BAT) in the context of obesity prevention and therapy. Due to the unique expression of the uncoupling protein 1 (UCP1), BAT is capable of non‑shivering thermogenesis, also defined as a metabolic heat production, related to increased metabolic rate. All processes that contribute to an increase in activity and/or quantity of BAT are able to upturn metabolism, and thus enable the above therapeutic goals to be achieved. GCs may stimulate BAT differentiation and proliferation. In the case of differentiation, the opposite effect of GCs has been also described. Within white adipose tissue (WAT) GCs inhibit the formation of so called beige adipocytes that are functionally and morphologically similar to the adipocytes from BAT. The activity of GCs with concomitant inhibition of WAT browning is mediated by the induction of microRNA-27b (MIR27B) expression. GCs are responsible for the decline in BAT activity as the body ages. Depriving the body of an enzyme responsible for local reduction of cortisone into an active GC‑cortisol in BAT (11β‑hydroxysteroid dehydrogenase type 1; 11β‑HSD1) prevents the reduction of BAT activity. The effects of high doses of GCs on BAT generally depend on the exposure time. Prolonged elevation in GCs level decreases BAT activity. During adrenergic stimulation the effect of GCs on BAT is ambiguous, because both decrease and increase in activity has been described. A full understanding of the GCs impact on brown remodeling in WAT may reveal a discovery of a novel preventive and therapeutic strategies for obesity and possibly other metabolic disorders.

Enlargement of Interscapular Brown Adipose Tissue in Growth Hormone Antagonist Transgenic and in Growth Hormone Receptor Gene-Disrupted Dwarf Mice

2003 ◽  
Vol 228 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Yuesheng Li ◽  
Joanne R. Knapp ◽  
John J. Kopchick
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
The Body ◽  
Northern Analysis ◽  
Interscapular Brown Adipose Tissue ◽  
Triglyceride Accumulation ◽  
Brown Adipose ◽  
Dwarf Mice

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.

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.

Effects of rate of blood flow on fractional extraction and on uptake of infused noradrenaline by brown adipose tissue in vivo

1980 ◽  
Vol 58 (10) ◽  
pp. 1212-1220 ◽  
Author(s):  
David O. Foster ◽  
Florent Depocas ◽  
Gloria Zaror-Behrens ◽  
M. Lorraine Frydman ◽  
Suzanne Lacelle
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Major Influence ◽  
Interscapular Brown Adipose Tissue ◽  
Diffusion Limited ◽  
Brown Adipose ◽  
Arterial Plasma ◽  
Response Percentage

The rate of blood flow (Q) to interscapular brown adipose tissue (IBAT) and the arteriovenous difference in plasma noradrenaline (NA) across the tissue were measured in warm-acclimated (WA) or cold-acclimated (CA) rats during infusion of NA at doses of 1–12.5 ng min−1 g−0.74 (approximately 0.2–2.7 μg min−1 kg−1) and in the period of steady calorigenic response associated with steady concentration of NA in arterial plasma (ANA). ANA was linearly related to the dose of NA. Calorigenic response, percentage of cardiac output to IBAT, and Q per gram of IBAT were sigmoid functions of ANA and at their maxima were about 2.5 times greater in CA than in WA rats. The rate of uptake of NA by IBAT increased with ANA and Q, each of which had a major influence on rate, but the coefficient of extraction of NA by the tissue (ENAIBAT) declined. Measurements in rats given a dose of propranolol that partially inhibited the NA-induced increase in Q to IBAT indicated that the decline in ENAIBAT was attributable primarily to the increase in Q rather than to increasing saturation of uptake mechanisms. Diffusion-limited extraction of NA is the probable basis for the effect of Q on ENAIBAT. Possible implications of flow-dependent extraction of NA in studies involving measurements of the uptake of exogenous NA by tissues or organs are discussed.

scholarly journals Relationship of brown adipose tissue perfusion and function: a study through β2-adrenoreceptor stimulation

2016 ◽  
Vol 120 (8) ◽  
pp. 825-832 ◽  
Author(s):  
Laura Ernande ◽  
Kristin I. Stanford ◽  
Robrecht Thoonen ◽  
Haihua Zhang ◽  
Maëva Clerte ◽  
...  
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
Direct Effect ◽  
Brown Adipocytes ◽  
Bat Activity ◽  
Brown Adipose

Brown adipose tissue (BAT) activation increases glucose and lipid consumption; as such, it is been considered as a potential therapy to decrease obesity. BAT is highly vascularized and its activation is associated with a necessary increase in blood flow. However, whether increasing BAT blood flow per se increases BAT activity is unknown. To examine this hypothesis, we investigated whether an isolated increase in BAT blood flow obtained by β2-adrenoreceptor (β2-AR) stimulation with salbutamol increased BAT activity. BAT blood flow was estimated in vivo in mice using contrast-enhanced ultrasound. The absence of direct effect of salbutamol on the function of isolated brown adipocytes was assessed by measuring oxygen consumption. The effect of salbutamol on BAT activity was investigated by measuring BAT glucose uptake in vivo. BAT blood flow increased by 2.3 ± 0.6-fold during β2-AR stimulation using salbutamol infusion in mice ( P = 0.003). β2-AR gene expression was detectable in BAT but was extremely low in isolated brown adipocytes. Oxygen consumption of isolated brown adipocytes did not change with salbutamol exposure, confirming the absence of a direct effect of β2-AR agonist on brown adipocytes. Finally, β2-AR stimulation by salbutamol increased BAT glucose uptake in vivo (991 ± 358 vs. 135 ± 49 ng glucose/mg tissue/45 min in salbutamol vs. saline injected mice, respectively, P = 0.046). In conclusion, an increase in BAT blood flow without direct stimulation of the brown adipocytes is associated with increased BAT metabolic activity. Increasing BAT blood flow might represent a new therapeutic target in obesity.

scholarly journals Brown adipose tissue development and function and its impact on reproduction

2018 ◽  
Vol 238 (1) ◽  
pp. R53-R62 ◽  
Author(s):  
Michael E Symonds ◽  
Peter Aldiss ◽  
Neele Dellschaft ◽  
James Law ◽  
Hernan P Fainberg ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Maternal Obesity ◽  
Thermal Environment ◽  
Uncoupling Protein ◽  
The Body ◽  
Substantial Impact ◽  
Brown Adipose ◽  
Fat Depot

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.

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.

Thermogenic effects of dihydrocodeine in the rat

1988 ◽  
Vol 66 (1) ◽  
pp. 61-65 ◽  
Author(s):  
Nancy J. Rothwell ◽  
Michael J. Stock ◽  
Alison E. Tedstone
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Opiate Receptors ◽  
Zucker Rats ◽  
Tissue Blood Flow ◽  
Dependent Manner ◽  
Brown Adipose ◽  
Adrenergic Antagonist

The object of this study was to assess the effects of dihydrocodeine on thermogenesis and brown adipose tissue activity in the rat from measurements of oxygen consumption and blood flow. Acute injection of dihydrocodeine tartrate (s.c.) stimulated resting oxygen consumption [Formula: see text] in Sprague–Dawley rats in a dose-dependent manner (0.5–50 mg/kg), with a peak response (40–45% increase) occurring at 10–25 mg/kg. This effect was also observed in urethane-anaesthetized rats (although the effect was reduced) and in conscious animals following gastric intubation with the drug. Pretreatment of rats with either a β-adrenergic antagonist (propranolol, 20 mg/kg), ACTH (4 g/kg), or an opiate antagonist (WIN44441-1, 2 mg/kg) significantly reduced the response to dihydrocodeine, whereas corticosterone injection (5 mg/kg) enhanced the effect. Surgical adrenalectomy or hypophysectomy (HYPX) almost completely abolished the thermogenic effect of dihydrocodeine. Dihydrocodeine also stimulated [Formula: see text] in lean (58% increase) and genetically obese Zucker rats (69% increase), and in both Zucker genotypes these responses were only slightly affected by HYPX, but enhanced in HYPX rats treated daily with corticosterone (1 mg/kg). Tissue blood flow, assessed from the distribution of radiolabelled microspheres, was unaffected in white adipose tissue, skeletal muscle, testes, kidney, brain, and liver (arterial supply) after a single injection of dihydrocodeine (25 mg/kg), but flow to interscapular and perirenal brown adipose tissue was increased by 9- to 10-fold. Surgical sympathectomy of brown adipose tissue prevented the increase in blood flow. These potent thermogenic effects of dihydrocodeine in the rat appear to result from sympathetic activation of heat production in brown fat and to involve opiate receptors, but can also be modified by pituitary and (or) adrenal hormones.

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.

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