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.

Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo

1986 ◽  
Vol 64 (5) ◽  
pp. 609-614 ◽  
Author(s):  
Stephanie W. Y. Ma ◽  
David O. Foster
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Tissue Blood Flow ◽  
Glycerol Release ◽  
Maximal Stimulation ◽  
Brown Adipose ◽  
Lactate And Pyruvate

The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 μmol/min) and release of glycerol (0.9 and 1.2 μmol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 μmol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation. Both in absolute terms and in relation to the export of glycerol the in vivo export of fatty acids from the adipocytes of IBAT was much less than is observed with brown adipocytes in vitro.

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 A tissue-specific increase in lipogenesis in rat brown adipose tissue in hypothyroidism

1988 ◽  
Vol 251 (2) ◽  
pp. 553-557 ◽  
Author(s):  
H S Baht ◽  
E D Saggerson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Maximum Activity ◽  
Brown Adipocyte ◽  
Glycolytic Flux ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Brown Adipose

1. Rats were made hypothyroid by feeding them with propylthiouracil together with a low-iodine diet for 4 weeks. 2. [U-14C]Glucose conversion into fatty acids was substantially enhanced in brown adipocytes isolated from hypothyroid rats. Incorporation of 3H2O into fatty acids in vivo was enhanced in hypothyroidism in interscapular brown fat, but not in epididymal white fat or in liver. Hypothyroidism increased the activities of fatty acid synthase and ATP citrate lyase in brown, but not in white, adipocytes. 3. Glycolytic flux in brown adipocytes, quantified by [3-3H]glucose detritiation, was increased by hypothyroidism. This change was accompanied by increased maximum activity of phosphofructokinase. In white adipocytes a large increase in phosphofructokinase maximum activity was observed in hypothyroidism, but this change was accompanied by only small increases in the rate of glucose detritiation by incubated cells. It is suggested that in the brown adipocyte the overall conversion of glucose into fatty acids is enhanced in thyroid deficiency, but that this change is muted in the white adipocyte, possibly because of limitation of glucose transport. 4. Fatty acid synthesis in brown adipocytes from hypothyroid animals was considerably less sensitive to inhibition by exogenous fatty acids than is the process in cells from euthyroid animals. Consequently, the effect of hypothyroidism to enhance lipogenesis is amplified in the presence of physiological concentrations of fatty acid.

scholarly journals The effects of melatonin administration in different times of day on the brown adipose tissue in rats with high-calorie diet-induced obesity

2019 ◽  
Vol 77 (1) ◽  
pp. 55-61 ◽  
Author(s):  
O. Kalmykova ◽  
M. Dzerzhynsky
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Optical Density ◽  
Lipid Droplets ◽  
Brown Adipocytes ◽  
Melatonin Administration ◽  
Brown Adipose ◽  
Calorie Diet ◽  
Evening Administration ◽  
High Calorie

The aim of our study was to determine morpho-functional state (area of nucleus, brown adipocytes and also area and number of lipid droplets in each cells, general optical density of tissue) of brown adipose tissue in rats with high-calorie (high fat) dietinduced obesity after melatonin administration in different time of the day (morning and evening). Melatonin was administered daily by gavage for 7 weeks in dose 30 mg/kg either 1 h after lights-on (ZT01) or 1 h before lights-off (ZT11) rats with high-calorie diet (HCD). Besides morphometric parameters as well were measured related visceral fat weight and related brown adipose tissue mass. Rats with HCD had huge changes in brown adipocytes morphology, which summarized in become resembles of classical white adipocytes: grown lipid droplets and cells area, but goes down lipid droplets number and optical density of brown adipose tissue. In general brown adipose tissue with above mentioned characteristic from HCD rats lose their ability to conduct strongly thermoproduction function. After melatonin used in rats with HCD arise leveling of pathological changes, which associated with consumption of HCD. Namely, in groups HCD ZT01 and HCD ZT11 we obtain decreased cells and lipid droplets area, increased lipid droplets number and optical density of brown adipose tissue, in relation to group HCD. Therese received changes has evidence about functionally active brown adipose tissue state, which can also dissipate of exceed energy (lipids – triacylglycerols) amount into whole organism during heat production for avoid to its storage in white adipose tissue and in outside adipose tissue. In addition, evening administration of melatonin (group HCD ZT11) demonstrate more activated state of brown adipose tissueand also related visceral weight gain less, than morning(group HCD ZT01). In conclusions, melatonin influence on morpho-functional state brown adipose tissue in rats with HCD, moreover evening administration can use for obesity therapy via its strong action on activate brown adipocytes.

scholarly journals Allosteric regulation of thioesterase superfamily member 1 by lipid sensor domain binding fatty acids and lysophosphatidylcholine

2020 ◽  
Vol 117 (36) ◽  
pp. 22080-22089 ◽  
Author(s):  
Matthew C. Tillman ◽  
Norihiro Imai ◽  
Yue Li ◽  
Manoj Khadka ◽  
C. Denise Okafor ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipid Droplets ◽  
Enzymatic Reaction ◽  
Lipid Transfer ◽  
Brown Adipose ◽  
Start Domain ◽  
Lipid Sensor ◽  
Long Chain

Nonshivering thermogenesis occurs in brown adipose tissue to generate heat in response to cold ambient temperatures. Thioesterase superfamily member 1 (Them1) is transcriptionally up-regulated in brown adipose tissue upon exposure to the cold and suppresses thermogenesis in order to conserve energy reserves. It hydrolyzes long-chain fatty acyl-CoAs that are derived from lipid droplets, preventing their use as fuel for thermogenesis. In addition to its enzymatic domains, Them1 contains a C-terminal StAR-related lipid transfer (START) domain with unknown ligand or function. By complementary biophysical approaches, we show that the START domain binds to long-chain fatty acids, products of Them1’s enzymatic reaction, as well as lysophosphatidylcholine (LPC), lipids shown to activate thermogenesis in brown adipocytes. Certain fatty acids stabilize the START domain and allosterically enhance Them1 catalysis of acyl-CoA, whereas 18:1 LPC destabilizes and inhibits activity, which we verify in cell culture. Additionally, we demonstrate that the START domain functions to localize Them1 near lipid droplets. These findings define the role of the START domain as a lipid sensor that allosterically regulates Them1 activity and spatially localizes it in proximity to the lipid droplet.

Rare fatty acids in brown fat are substrates for thermogenesis during arousal from hibernation

1989 ◽  
Vol 256 (1) ◽  
pp. R146-R154 ◽  
Author(s):  
C. Carneheim ◽  
B. Cannon ◽  
J. Nedergaard
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Brown Adipose Tissue ◽  
Acid Composition ◽  
Brown Fat ◽  
Brown Adipose ◽  
Tissue Lipids

Because brown adipose tissue lipids are the preferred substrate for thermogenesis during arousal from hibernation, the fatty acid composition of brown fat lipids was followed during cold acclimation and during a hibernation bout. In control golden hamsters (living at 22 degrees C), the fatty acid composition of the white adipose tissue closely resembled that of the food, but brown adipose tissue contained more animal-derived fatty acids. As an effect of acclimation to cold, the fatty acid composition of brown adipose tissue changed to resemble that of the food, and no marked differences between white and brown adipose tissue were then evident. During a hibernation bout, a major part of the fatty acids accumulated in brown fat during entry into hibernation consisted of "rare" acids, such as homo-gamma-linoleic acid. Homo-gamma-linoleic, together with eicosadienoic acid and lignoceric acid, was preferentially utilized during the early phase of arousal. During this phase, "bulk" fatty acids, such as linoleic acid, were spared, whereas in late arousal, linoleic acid was the preferred substrate. It was concluded that rare fatty acids are of quantitative significance in brown adipose tissue during hibernation and arousal.

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 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 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.

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