scholarly journals Regulation of rat foetal lipogenesis in brown adipose tissue in vivo and in isolated brown adipocytes during the last day of, and after prolonged, gestation

1987 ◽  
Vol 243 (2) ◽  
pp. 617-620 ◽  
Author(s):  
C Roncero ◽  
M Lorenzo ◽  
M Benito
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Incubation Medium ◽  
Brown Adipocyte ◽  
Isolated Cells ◽  
Pregnant Rats ◽  
Brown Adipocytes ◽  
Brown Adipose

Rates of lipogenesis in foetal isolated brown adipocytes from 22-day-pregnant rats were significantly increased by lactate plus pyruvate as major substrates in the incubation medium, in comparison with the endogenous rates. Insulin stimulated foetal brown-adipocyte lipogenesis, and adrenaline or noradrenaline and isoprenaline decreased lipogenesis. Glucagon had no effect on the lipogenic rate in brown adipocytes. Progesterone administration to the mother significantly increased the rates of lipogenesis in brown adipose tissue and in isolated brown adipocytes from 22-day foetuses. Prolongation of gestation by progesterone to day 23 decreased the rates of brown-adipose-tissue lipogenesis in vivo and in isolated cells in the post-mature foetuses.

scholarly journals Effects of hypothyroidism and hyperthyroidism on GDP binding to brown-adipocyte mitochondria from rats

1989 ◽  
Vol 263 (2) ◽  
pp. 341-345 ◽  
Author(s):  
J A Woodward ◽  
E D Saggerson
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Dna Content ◽  
Brown Adipocyte ◽  
Thyroid Status ◽  
Mitochondrial Uncoupling ◽  
Brown Adipocytes ◽  
Period 2 ◽  
Brown Adipose

1. Rats were made hypothyroid by giving them a low-iodine diet with propylthiouracil for 4 weeks, or were made hyperthyroid by injection with tri-iodothyronine (T3) over a 3-day period. 2. Brown adipocytes were isolated from the interscapular depots of these animals or from their euthyroid controls, followed by isolation of mitochondria from the cells. 3. Relative to cell DNA content, hypothyroidism decreased the maximum binding (Bmax.) of [3H]GDP to mitochondria by 50%. T3 treatment increased binding by 37%. 4. These findings, which are discussed in relation to previously observed changes in brown adipose tissue after alteration of thyroid status, suggest that mitochondrial uncoupling for thermogenesis is less or more effective in hypothyroidism or hyperthyroidism respectively.

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 Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice

2020 ◽  
Vol 4 (1) ◽  
pp. e202000924
Author(s):  
Ruth Karlina ◽  
Dominik Lutter ◽  
Viktorian Miok ◽  
David Fischer ◽  
Irem Altun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Expression Profiles ◽  
Stromal Vascular Fraction ◽  
Gene Expression Profiles ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Brown Adipose

Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. Although increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Recently, UCP1 high and low expressing brown adipocytes were identified, but a developmental origin of these subtypes has not been studied. To obtain more insights into brown preadipocyte heterogeneity, we use single-cell RNA sequencing of the BAT stromal vascular fraction of C57/BL6 mice and characterize brown preadipocyte and adipocyte clonal cell lines. Statistical analysis of gene expression profiles from brown preadipocyte and adipocyte clones identify markers distinguishing brown adipocyte subtypes. We confirm the presence of distinct brown adipocyte populations in vivo using the markers EIF5, TCF25, and BIN1. We also demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that BIN1 marks dormant brown adipocytes. The existence of multiple brown adipocyte subtypes suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct functions in thermogenesis and the regulation of whole body energy homeostasis.

scholarly journals Immunohistochemical identification of the uncoupling protein in rat brown adipose tissue.

1985 ◽  
Vol 33 (2) ◽  
pp. 150-154 ◽  
Author(s):  
M Cadrin ◽  
M Tolszczuk ◽  
J Guy ◽  
G Pelletier ◽  
K B Freeman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Staining Technique ◽  
Cellular Heterogeneity ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Immunohistochemical Technique ◽  
Brown Adipose ◽  
Pap Method

Brown adipose tissue mitochondria are characterized by the presence of an uncoupling protein that gives them an exceptional capacity for substrate-controlled respiration and thermogenesis. The specific localization of this protein in rat brown adipocytes was demonstrated using an immunohistochemical technique, the peroxidase-antiperoxidase (PAP) method. Light microscopy observations showed that serum antibodies raised against the uncoupling protein selectively reacted with multilocular brown adipocytes. No labeling could be detected in either unilocular adipocytes, capillaries, or muscle fibers (striated and vascular smooth muscle). Staining was more intensive in certain adipocytes than in others, suggesting the presence of cellular heterogeneity. The specificity of the staining technique was demonstrated by showing that treatment of the preparations with antiserum saturated with an excess of uncoupling protein almost entirely inhibited brown adipocyte labeling. The specificity and selectivity of the PAP method allow the clear differentiation of uncoupling protein-containing adipocytes from other cellular types, suggesting that this immunohistochemical technique will represent an extremely useful tool for studying adipocyte function and differentiation.

scholarly journals Regulation of mitochondrial biogenesis in brown adipose tissue: nuclear respiratory factor-2/GA-binding protein is responsible for the transcriptional regulation of the gene for the mitochondrial ATP synthase β subunit

1998 ◽  
Vol 331 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Josep A. VILLENA ◽  
Octavi VIÑAS ◽  
Teresa MAMPEL ◽  
Roser IGLESIAS ◽  
Marta GIRALT ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Adipocyte Differentiation ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Nuclear Respiratory Factor ◽  
Brown Adipose ◽  
Nuclear Respiratory Factor 2 ◽  
Ga Binding Protein

The regulation of transcription of the gene for the β subunit of the FoF1 ATP synthase (ATPsynβ) in brown adipose tissue has been studied as a model to determine the molecular mechanisms for mitochondrial biogenesis associated with brown adipocyte differentiation. The expression of the ATPsynβ mRNA is induced during the brown adipocyte differentiation that occurs during murine prenatal development or when brown adipocytes differentiate in culture. This induction occurs in parallel with enhanced gene expression for other nuclear and mitochondrially-encoded components of the respiratory chain/oxidative phosphorylation system (OXPHOS). Transient transfection assays indicated that the expression of the ATPsynβ gene promoter is higher in differentiated HIB-1B brown adipocytes than in non-differentiated HIB-1B cells. A major transcriptional regulatory site was identified between nt -306 and -266 in the ATPsynβ promoter. This element has a higher enhancer capacity in differentiated brown adipocyte HIB-1B cells than in non-differentiated cells. Electrophoretic shift analysis indicated that Sp1and nuclear respiratory factor-2/GA-binding protein (NRF2/GABP) were the main nuclear proteins present in brown adipose tissue that bind this site. Double-point mutant analysis indicated a major role for the NRF2/GABP site in the enhancer capacity of this element in brown fat cells. It is proposed that NRF2/GABP plays a pivotal role in the co-ordinated enhancement of OXPHOS gene expression associated with mitochondrial biogenesis in brown adipocyte differentiation.

scholarly journals Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function

2016 ◽  
Vol 36 (15) ◽  
pp. 2027-2038 ◽  
Author(s):  
Hongyi Zhou ◽  
Stephen M. Black ◽  
Tyler W. Benson ◽  
Neal L. Weintraub ◽  
Weiqin Chen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Endoplasmic Reticulum Membrane ◽  
Brown Adipocytes ◽  
White Adipocyte ◽  
Brown Adipose ◽  
And Function

Brown adipose tissue (BAT) plays a unique role in regulating whole-body energy homeostasis by dissipating energy through thermogenic uncoupling. Berardinelli-Seip congenital lipodystrophy (BSCL) type 2 (BSCL2; also known as seipin) is a lipodystrophy-associated endoplasmic reticulum membrane protein essential for white adipocyte differentiation. Whether BSCL2 directly participates in brown adipocyte differentiation, development, and function, however, is unknown. We show that BSCL2 expression is increased during brown adipocyte differentiation. Its deletion does not impair the classic brown adipogenic program but rather induces premature activation of differentiating brown adipocytes through cyclic AMP (cAMP)/protein kinase A (PKA)-mediated lipolysis and fatty acid and glucose oxidation, as well as uncoupling. cAMP/PKA signaling is physiologically activated during neonatal BAT development in wild-type mice and greatly potentiated in mice with genetic deletion ofBscl2in brown progenitor cells, leading to reduced BAT mass and lipid content during neonatal brown fat formation. However, prolonged overactivation of cAMP/PKA signaling during BAT development ultimately causes apoptosis of brown adipocytes through inflammation, resulting in BAT atrophy and increased overall adiposity in adult mice. These findings reveal a key cell-autonomous role for BSCL2 in controlling BAT mass/activity and provide novel insights into therapeutic strategies targeting cAMP/PKA signaling to regulate brown adipocyte function, viability, and metabolic homeostasis.

scholarly journals Lipid Droplets in Brown Adipose Tissue Are Dispensable for Cold-Induced Thermogenesis

2020 ◽  
Author(s):  
Chandramohan Chitraju ◽  
Alexander Fischer ◽  
Robert V. Farese ◽  
Tobias C. Walther
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Lipid Droplets ◽  
Metabolic Energy ◽  
Brown Adipocyte ◽  
Glucose Disposal ◽  
Brown Adipocytes ◽  
Brown Adipose

SUMMARYBrown adipocytes store metabolic energy as triglycerides (TG) in multilocular lipid droplets (LDs). Fatty acids released from brown adipocyte LDs by lipolysis are thought to activate and fuel UCP1-mediated thermogenesis. Here we test this hypothesis by preventing fatty acid storage in murine brown adipocytes through brown adipose tissue (BAT)-specific deletions of the TG synthesis enzymes, DGAT1 and DGAT2 (BA-DGAT KO). Despite the absence of LDs, BA-DGAT KO mice had functional BAT and maintained euthermia during acute or chronic cold exposure. As apparent adaptations to the lack of TG, brown adipocytes of BA-DGAT KO mice appear to utilize circulating glucose and fatty acids, as well as stored glycogen to fuel thermogenesis. Moreover, BA-DGAT KO mice were resistant to diet-induced glucose intolerance, likely due to increased glucose disposal by BAT. Thus, surprisingly, TGs in BAT are dispensable for its function, in part through adaptations to utilize other fuel sources.

Brown adipose tissue hyperplasia: a fundamental mechanism of adaptation to cold and hyperphagia

1982 ◽  
Vol 242 (6) ◽  
pp. E353-E359 ◽  
Author(s):  
L. Bukowiecki ◽  
A. J. Collet ◽  
N. Follea ◽  
G. Guay ◽  
L. Jahjah
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Acclimation ◽  
Cold Exposure ◽  
Interstitial Cells ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Interscapular Brown Adipose Tissue ◽  
Blood Capillaries ◽  
Brown Adipose

Cold acclimation (4 degrees C) and "cafeteria diets" increased the thermic response of rats to catecholamines. This phenomenon was accompanied by six- to eightfold increases of interscapular brown adipose tissue (IBAT) weight, total tissue cytochrome oxidase activity, and total number of brown adipocytes. Quantitative radioautographic experiments using [3H]thymidine disclosed that cold exposure markedly enhanced the mitotic activity in blood capillaries and small-venule endothelial cells, adipose tissue interstitial cells, and preadipocytes rather than in fully differentiated brown adipocytes. IBAT mitotic index increased 70 times over control values after only 2 days of cold exposure. Thereafter, the proliferative activity progressively decreased. IBAT cell composition was modified during cold acclimation as the percentage of interstitial cells and preadipocytes increased over the other cellular types. Because brown adipose tissue is the principal site of norepinephrine-induced thermogenesis in homeothermal animals, it is suggested that brown adipocyte proliferation from precursor cells represents the fundamental phenomenon explaining the increased capacity of cold-acclimated animals to respond calorigenically to catecholamines.

scholarly journals Unravelling the developmental roadmap towards human brown adipose tissue

2020 ◽  
Author(s):  
Stefania Carobbio ◽  
Anne-Claire Guenantin ◽  
Myriam Bahri ◽  
Isabella Samuelson ◽  
Floris Honig ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Pluripotent Stem Cells ◽  
Therapeutic Strategy ◽  
Paraxial Mesoderm ◽  
Brown Adipocyte ◽  
Diabetic Patients ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
And Function

AbstractIncreasing brown adipose tissue (BAT) mass and activation has been proposed as a potential therapeutic strategy to treat obesity and associated cardiometabolic complications. Given that obese and diabetic patients possess low amounts of BAT, an efficient way to expand their BAT mass would be necessary if BAT is to be useful. Currently, there is limited knowledge about how human BAT develops, differentiates, and is optimally activated. Moreover, to have access to human BAT is challenging, given its low volume and being anatomically dispersed. These constrain makes detailed mechanistic studies related to BAT development and function in humans virtually impossible. To overcome these limitations, we have developed a human-relevant new protocol for the differentiation of human pluripotent stem cells (hPSCs) into brown adipocytes (BAs). Unique to this protocol is that it is chemically-defined to recapitulate a physiological step-by-step developmental path of BAT that captures transient paraxial mesoderm and BAT progenitor states, on its way to reaching the adipocyte stage finally. These hPSC-derived BAs express brown adipocyte and thermogenic markers, are insulin sensitive, and respond to β-adrenergic stimuli. This new protocol is a scalable tool to study human BAs during development.

Defective metabolic effects of norepinephrine and insulin in obese Zucker rat brown adipose tissue

1990 ◽  
Vol 258 (2) ◽  
pp. E320-E328
Author(s):  
A. Marette ◽  
A. Geloen ◽  
A. Collet ◽  
L. J. Bukowiecki
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Transport ◽  
Metabolic Effects ◽  
Brown Adipocyte ◽  
Zucker Rats ◽  
Maximal Velocity ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Obese Rats

The effects of insulin and norepinephrine on oxygen consumption, lipolysis, and glucose transport were investigated in adipocytes isolated from brown adipose tissue (BAT) of adult (4-5 mo) lean (Fa/?) and obese (fa/fa) Zucker rats. Total BAT protein content and cytochrome oxidase activity were similar in both phenotypes, suggesting that obese rats have a normal mitochondrial content. Light and electron micrographs revealed that brown adipocytes from obese rats contained very large multilocular triglyceride droplets, but their mitochondrial ultrastructure was normal. Norepinephrine, when added in excess (1 microM), stimulated brown adipocyte respiration 8-10 times above basal levels both in lean and obese animals. However, dose-response experiments disclosed that the 50% effective concentration (EC50) was significantly higher in cells isolated from obese rats compared with lean ones (EC50 115 vs. 43 nM, P less than 0.05). The lipolytic sensitivity to norepinephrine was also reduced in adipocytes isolated from obese animals (EC50 83 vs. 12 nM, P less than 0.05). Addition of dibutyryl adenosine 3',5'-cyclic monophosphate to respiring obese rat brown adipocytes restored to normal the defective response to norepinephrine, suggesting that the reduction in catecholamine sensitivity resulted from a deactivation of the receptor-adenylate cyclase complex. On the other hand, the antilipolytic and antithermogenic actions of physiological concentrations of insulin were significantly reduced in obese BAT cells. The sensitivity and responsiveness of obese rat brown adipocytes for insulin-stimulated glucose transport were also markedly decreased (EC50 1 vs. 0.3 nM, P less than 0.05; maximal velocity 3-fold vs. 7-fold).(ABSTRACT TRUNCATED AT 250 WORDS)

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