scholarly journals Effect of brown adipose tissue/cells on the growth of mouse hepatocellular carcinoma in�vitro and in�vivo

2019 ◽  
Author(s):  
Dong Liu ◽  
Yi Li ◽  
Yue Shang ◽  
Wendie Wang ◽  
Shu‑Zhen Chen
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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Francesca-Maria Raffaelli ◽  
Julia Resch ◽  
Rebecca Oelkrug ◽  
K. Alexander Iwen ◽  
Jens Mittag

AbstractBrown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.


2003 ◽  
Vol 285 (1) ◽  
pp. R177-R182 ◽  
Author(s):  
W. T. L. Festuccia ◽  
N. H. Kawashita ◽  
M. A. R. Garofalo ◽  
M. A. F. Moura ◽  
S. R. C. Brito ◽  
...  

Brown adipose tissue (BAT) glyceroneogenesis was evaluated in rats either fasted for 48 h or with streptozotocin-diabetes induced 3 days previously or adapted for 20 days to a high-protein, carbohydrate-free (HP) diet, conditions in which BAT glucose utilization is reduced. The three treatments induced an increase in BAT glyceroneogenic activity, evidenced by increased rates of incorporation of [1-14C]pyruvate into triacylglycerol (TAG)-glycerol in vitro and a marked, threefold increase in the activity of BAT phospho enolpyruvate carboxykinase (PEPCK). BAT glycerokinase activity was not significantly affected by fasting or diabetes. After unilateral BAT denervation of rats fed either the HP or a balanced diet, glyceroneogenesis activity increased in denervated pads, evidenced by increased rates of nonglucose carbon incorporation into TAG-glycerol in vivo (difference between 3H2O and [14C]glucose incorporations) and of [1-14C]pyruvate in vitro. PEPCK activity was not significantly affected by denervation. The data suggest that BAT glyceroneogenesis is not under sympathetic control but is sensitive to hormonal/metabolic factors. In situations of reduced glucose use there is an increase in BAT glyceroneogenesis that may compensate the decreased generation of glycerol-3-phosphate from the hexose.


1968 ◽  
Vol 46 (6) ◽  
pp. 897-902 ◽  
Author(s):  
Barbara A. Horwitz ◽  
Paul A. Herd ◽  
Robert Emrie Smith

Examination of the in vivo effect of 2,4-dinitrophenol (DNP) on the brown adipose tissue of cold-exposed rats, as well as the in vitro response of this tissue to DNP and dicumarol, indicates that brown fat does possess a functional electron transport coupled phosphorylating system. Moreover, the fact that a norepinephrine-induced thermogenic response (in vivo) can be elicited from the brown fat after DNP administration implies that the effect of norepinephrine (NE) is not primarily due either to a physiological uncoupling by fatty acids, the level of which is increased by NE, or to stimulation of an ATP-ase system. Alternatively, our data suggest that under basal conditions (i.e. when the animal is not stimulated by cold stress or NE), the heat production (oxygen consumption) of the brown fat is limited by the availability of substrate rather than ADP. It is thus proposed that the thermogenic effect of NE results from the stimulation of lipolysis and an attendant increase of substrate available for oxidation.


2013 ◽  
Vol 51 (3) ◽  
pp. T75-T85 ◽  
Author(s):  
Stefania Carobbio ◽  
Barry Rosen ◽  
Antonio Vidal-Puig

Confirmation of the presence of functional brown adipose tissue (BAT) in humans has renewed interest in investigating the potential therapeutic use of this tissue. The finding that its activity positively correlates with decreased BMI, decreased fat content, and augmented energy expenditure suggests that increasing BAT mass/activity or browning of white adipose tissue (WAT) could be a strategy to prevent or treat obesity and its associated morbidities. The challenge now is to find a safe and efficient way to develop this idea. Whereas BAT has being widely studied in murine models bothin vivoandin vitro, there is an urgent need for human cellular models to investigate BAT physiology and functionality from a molecular point of view. In this review, we focus on the latest insights surrounding BAT development and activation in rodents and humans. Then, we discuss how the availability of murine models has been essential to identify BAT progenitors and trace their lineage. Finally, we address how this information can be exploited to develop human cellular models for BAT differentiation/activation. In this context, human embryonic stem and induced pluripotent stem cells-based cellular models represent a resource of great potential value, as they can provide a virtually inexhaustible supply of starting material for functional genetic studies, -omics based analysis and validation of therapeutic approaches. Moreover, these cells can be readily genetically engineered, opening the possibility of generating patient-specific cellular models, allowing the investigation of the influence of different genetic backgrounds on BAT differentiation in pathological or in physiological states.


2009 ◽  
Vol 296 (5) ◽  
pp. R1327-R1335 ◽  
Author(s):  
William T. Festuccia ◽  
Pierre-Gilles Blanchard ◽  
Véronique Turcotte ◽  
Mathieu Laplante ◽  
Meltem Sariahmetoglu ◽  
...  

We investigated the mechanisms whereby peroxisome proliferator-activated receptor-γ (PPARγ) agonism affects glucose and lipid metabolism in brown adipose tissue (BAT) by studying the impact of PPARγ activation on BAT glucose uptake and metabolism, lipogenesis, and mRNA levels plus activities of enzymes involved in triacylglycerol (TAG) synthesis. Interscapular BAT of rats treated or not with rosiglitazone (15 mg·kg−1·day−1, 7 days) was evaluated in vivo for glucose uptake and lipogenesis and in vitro for glucose metabolism, gene expression, and activities of glycerolphosphate acyltransferase (GPAT), phosphatidate phosphatase-1 (PAP or lipin-1), and diacylglycerol acyltransferase (DGAT). Rosiglitazone increased BAT mass without affecting whole tissue glucose uptake. BAT glycogen content (−80%), its synthesis from glucose (−50%), and mRNA levels of UDP-glucose pyrophosphorylase (−40%), which generates UDP-linked glucose for glycogen synthesis, were all reduced by rosiglitazone. In contrast, BAT TAG-glycerol synthesis in vivo and glucose incorporation into TAG-glycerol in vitro were stimulated by the agonist along with the activities and mRNA levels of glycerol 3-phosphate-generating phosphoenolpyruvate carboxykinase and glycerokinase. Furthermore, rosiglitazone markedly increased the activities of GPAT and DGAT but not those of lipin-1-mediated PAP-1, enzymes involved in the sequential acylation of glycerol 3-phosphate and TAG synthesis. Because an adequate supply of fatty acids is essential for BAT nonshivering thermogenesis, the enhanced ability of BAT to synthesize TAG under PPARγ activation may constitute an important mechanism by which lipid substrates are stored in preparation for an eventual thermogenic activation.


2018 ◽  
Author(s):  
Essam A. Assali ◽  
Anthony E. Jones ◽  
Michaela Veliova ◽  
Mahmoud Taha ◽  
Nathanael Miller ◽  
...  

AbstractA sharp increase in mitochondrial Ca2+ marks the activation of the brown adipose tissue (BAT) thermogenesis, yet the mechanisms preventing Ca2+ deleterious effects are poorly understood. Here, we show that adrenergic stimulation of BAT activates a PKA-dependent mitochondrial Ca2+ extrusion via the mitochondrial Na+/Ca2+ exchanger, NCLX. Adrenergic stimulation of NCLX-ablated brown adipocytes (BA) induces a profound mitochondrial Ca2+ overload and impaired uncoupled respiration. Core body temperature, PET imaging and VO2 measurements confirm a BAT specific thermogenic defect in NCLX-null mice.We show that mitochondrial Ca2+ overload induced by adrenergic stimulation of NCLX-null BAT, triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to remarkable mitochondrial swelling, Cytochrome c release and cell death in BAT. However, treatment with mPTP inhibitors rescue mitochondrial respiratory function and thermogenesis in NCLX-null BA, in vitro and in vivo.Our findings identify a novel pathway enabling non-lethal mitochondrial Ca2+ elevation during adrenergic stimulation of uncoupled respiration. Deletion of NCLX transforms the adrenergic pathway responsible for the stimulation of thermogenesis into a death pathway.


2018 ◽  
Vol 20 (9) ◽  
pp. 2264-2273 ◽  
Author(s):  
Peter Breining ◽  
Jonas B. Jensen ◽  
Elias I. Sundelin ◽  
Lars C. Gormsen ◽  
Steen Jakobsen ◽  
...  

1964 ◽  
Vol 207 (4) ◽  
pp. 840-844 ◽  
Author(s):  
G. Steiner ◽  
G. F. Cahill

Brown and white adipose tissue from rats exposed to 5 C for 9 days has been studied with reference to its composition and handling of glucose-U-C14 in vivo and in vitro. Brown adipose tissue from cold-exposed rats demonstrated a decreased lipid content per milligram nitrogen, due mainly to decreased amounts of neutral lipid with little change in phospholipid. The incorporation of glucose into neutral lipids, glyceride glycerol, and fatty acids was increased in vivo and in vitro. There was increased incorporation into CO2 in vitro and there was no change in glucose conversion to phospholipid in vivo. No changes in any of these were noted in epididymal fat pads. These findings suggest that cold exposure leads to alterations in carbohydrate metabolism and lipogenesis in brown adipose tissue but not in epididymal fat pads. The possible role in thermogenesis is discussed.


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