scholarly journals NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue

2021 ◽  
Vol 12 ◽  
Author(s):  
María Bové ◽  
Fermi Monto ◽  
Paloma Guillem-Llobat ◽  
M Dolores Ivorra ◽  
M Antonia Noguera ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Stem Cell Differentiation ◽  
Mrna Levels ◽  
Brown Adipocytes ◽  
Peripheral Tissues ◽  
Metabolic Functions ◽  
Neurotrophin 3 ◽  
Isolated Adipocytes

Neurotrophin-3 (NT3), through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (especially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 (encoded by NTF3) was present in human retroperitoneal AT and decreases with age. NT3 was also present in rat isolated adipocytes and retroperitoneal, interscapular, perivascular, and perirenal AT. Histological analysis evidences that NT3 was mainly present in vessels irrigating AT close associated to sympathetic fibers. Similar mRNA levels of TrkC (encoded by NTRK3) and β-adrenoceptors were found in all ATs assayed and in isolated adipocytes. NT3, through TrkC activation, exert a mild effect in lipolysis. Addition of NT3 during the differentiation process of human pre-adipocytes resulted in smaller adipocytes and increased uncoupling protein-1 (UCP-1) without changes in β-adrenoceptors. Similarly, transgenic mice with reduced expression of NT3 (Ntf3 knock-in lacZ reporter mice) or lacking endothelial NT3 expression (Ntf3flox1/flox2;Tie2-Cre+/0) displayed enlarged white and brown adipocytes and lower UCP-1 expression.ConclusionsNT3, mainly released by blood vessels, activates TrkC and regulates adipocyte differentiation and browning. Disruption of NT3/TrkC signaling conducts to hypertrophied white and brown adipocytes with reduced expression of the thermogenesis marker UCP-1.

scholarly journals NT3/TrkC pathway modulates the expression of UCP-1 and adipocyte size in human and murine adipose tissue

2020 ◽  
Author(s):  
María Bové ◽  
Fermi Monto ◽  
Paloma Guillem-Llobat ◽  
M Dolores Ivorra ◽  
M Antonia Noguera ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Stem Cell Differentiation ◽  
Mrna Levels ◽  
Brown Adipocytes ◽  
Peripheral Tissues ◽  
Metabolic Functions ◽  
Reporter Mice ◽  
Isolated Adipocytes

ABSTRACTNT3, through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (specially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 was present in human retroperitoneal AT and decreases with age. NT3 was also present in rat isolated adipocytes and retroperitoneal, interscapular, perivascular and perirenal AT. Histological analysis evidences that NT3 was mainly present in vessels irrigating AT close associated to sympathetic fibers. Similar mRNA levels of TrkC and β-adrenoceptors were found in all ATs assayed and in isolated adipocytes. NT3, through TrkC activation, exert a mild effect in lipolysis. Addition of NT3 during the differentiation process of human pre-adipocytes resulted in smaller adipocytes and increased uncoupling protein-1 (UCP-1) without changes in β-adrenoceptors. Similarly, transgenic mice with reduced expression of NT3 (Ntf3 knock-in lacZ reporter mice) or lacking endothelial NT3 expression (Ntf3flox1/flox2;Tie2-Cre+/0) displayed enlarged white and brown adipocytes and lower UCP-1 expression.ConclusionsNT3, mainly released by blood vessels, activates TrkC and regulates adipocyte differentiation and browning. Disruption of NT3/TrkC signaling conducts to hypertrophied white and brown adipocytes with reduced expression of the thermogenesis marker UCP-1

Growth factor regulation of uncoupling protein-1 mRNA expression in brown adipocytes

2002 ◽  
Vol 282 (1) ◽  
pp. C105-C112 ◽  
Author(s):  
Bibian García ◽  
Maria-Jesús Obregón
Keyword(s):  
Growth Factor ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Mrna Levels ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Proliferation And Differentiation ◽  
Epidermal Growth ◽  
Continuous Presence

To study the effect of the mitogens epidermal growth factor (EGF), acidic and basic fibroblast growth factors (aFGF and bFGF), and vasopressin on brown adipocyte differentiation, we analyzed the expression of uncoupling protein-1 (UCP-1) mRNA. Quiescent brown preadipocytes express high levels of UCP-1 mRNA in response to triiodothyronine (T3) and norepinephrine (NE). The addition of serum or the mitogenic condition aFGF + vasopressin + NE or EGF + vasopressin + NE decreases UCP-1 mRNA. A second addition of mitogens further decreases UCP-1 mRNA. Treatment with aFGF or bFGF alone increases UCP-1 mRNA, whereas the addition of EGF or vasopressin dramatically reduces UCP-1 mRNA levels. The continuous presence of T3 increases UCP-1 mRNA levels in cells treated with EGF, aFGF, or bFGF. The effect of T3 on the stimulation of DNA synthesis also was tested. T3 inhibits the mitogenic activity of aFGF and bFGF. In conclusion, mitogens like aFGF or bFGF allow brown adipocyte differentiation, whereas EGF and vasopressin inhibit the differentiation process. T3 behaves as an important hormone that regulates both brown adipocyte proliferation and differentiation.

scholarly journals Eicosapentaenoic Acid Increases Browning Markers in Subcutaneous Adipose Tissue and Primary Adipocytes from Wild Type and UCP-1 Deficient Mice (P15-007-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Shasika Jayarathne ◽  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
Shane Scoggin ◽  
Naima Moustaid-Moussa
Keyword(s):  
Adipose Tissue ◽  
Eicosapentaenoic Acid ◽  
Subcutaneous Adipose Tissue ◽  
Uncoupling Protein ◽  
Fibroblast Growth Factor 21 ◽  
Chow Diet ◽  
Mrna Levels ◽  
Wild Type ◽  
Brown Adipose ◽  
Subcutaneous Adipose

Abstract Objectives Brown adipose tissue (BAT) regulates energy balance through thermogenesis, in part via uncoupling protein -1 (UCP-1). White adipose tissue (WAT), namely subcutaneous adipose tissue (SAT) can convert to a beige/brite adipose tissue phenotype (browning) under thermogenic conditions such as cold. We previously reported that eicosapentaenoic acid (EPA) reduced obesity and glucose intolerance, and increased UCP-1 in BAT of B6 mice at ambient temperature (22°C); and these effects were attenuated at thermoneutral environment (28–30°C). We hypothesized that EPA exerts anti-obesity effects on SAT, including increased browning, adipocyte hypotrophy; and these effects require UCP-1. Methods Six-week-old B6 wild type (WT) and UCP-1 knock-out (KO) male mice were maintained at thermoneutral environment and fed high fat diet (HF) with or without 36 g/kg of AlaskOmega EPA-enriched fish oil (800 mg/g) for 14 weeks; and SAT was collected for histological, gene and protein analyses. SAT was also prepared from chow diet-fed WT and KO mice at ambient environment to prepare stroma vascular cells, which were differentiated into adipocytes, treated with 100uM EPA for 48 hours then harvested for mRNA and protein analyses. Results KO mice fed HF diets had the highest body weight (P < 0.05) among all groups. EPA reduced fat cell size in both WT and KO mice fed the EPA diet. mRNA levels of fibroblast growth factor-21 (FGF-21) were higher in SAT of WT mice fed EPA compared to WT mice fed HF (P < 0.05), with no differences between the KO genotype. KO mice fed HF diets had lower levels of UCP-3 in SAT compared to WT mice fed HF (P < 0.05), which was rescued only in the KO mice fed EPA (P < 0.05). UCP-1 protein levels were very low in SAT tissues, and UCP-2 mRNA levels were similar across all groups in SAT. Interestingly, EPA significantly (P < 0.05) increased mRNA expression of UCP-2, UCP-3 and FGF21 in differentiated SAT adipocytes from both WT and KO compared to control. Furthermore, UCP-1 mRNA levels were significantly higher in WT adipocytes treated with EPA, compared to non-treated cells (P < 0.05). Additional mechanistic studies are currently underway to further dissect adipose depot differences in EPA effects in WT vs. KO mice. Conclusions Our data suggest that EPA increases SAT browning, independently of UCP-1. Funding Sources NIH/NCCIH.

scholarly journals Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice

2018 ◽  
Vol 19 (10) ◽  
pp. 2904 ◽  
Author(s):  
Christian Carpéné ◽  
Saioa Gómez-Zorita ◽  
Alice Chaplin ◽  
Josep Mercader
Keyword(s):  
Adipose Tissue ◽  
Phosphoenolpyruvate Carboxykinase ◽  
De Novo ◽  
Uncoupling Protein ◽  
De Novo Lipogenesis ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Brown Adipose ◽  
High Sucrose ◽  
Sucrose Drinking

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.

scholarly journals SUN-587 IDH1-Dependent Alpha-KG Regulates Brown Fat Differentiation and Function by Modulating Histone Methylation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Won Kon Kim ◽  
Baek-Soo Han
Keyword(s):  
Histone Methylation ◽  
Molecular Mechanisms ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Ectopic Expression ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
And Function ◽  
Brown Adipogenesis

Abstract Brown adipocytes play important roles in the regulation of energy homeostasis by uncoupling protein 1-mediated non-shivering thermogenesis. Recent studies suggest that brown adipocytes as novel therapeutic targets for combating obesity and associated diseases, such as type II diabetes. However, the molecular mechanisms underlying brown adipocyte differentiation and function are not fully understood. We employed previous findings obtained through proteomic studies performed to assess proteins displaying altered levels during brown adipocyte differentiation. Here, we performed assays to determine the functional significance of their altered levels during brown adipogenesis and development. We identified isocitrate dehydrogenase 1 (IDH1) as upregulated during brown adipocyte differentiation, with subsequent investigations revealing that ectopic expression of IDH1 inhibited brown adipogenesis, whereas suppression of IDH1 levels promoted differentiation of brown adipocytes. Additionally, Idh1 overexpression resulted in increased levels of intracellular α-ketoglutarate (α-KG) and inhibited the expression of genes involved in brown adipogenesis. Exogenous treatment with α-KG reduced brown adipogenesis during the early phase of differentiation, and ChIP analysis revealed that IDH1-mediated α-KG reduced trimethylation of histone H3 lysine 4 in the promoters of genes associated with brown adipogenesis. Furthermore, administration of α-KG decreased adipogenic gene expression by modulating histone methylation in brown adipose tissues of mice. These results suggested that the IDH1–α-KG axis plays an important role in regulating brown adipocyte differentiation and might represent a therapeutic target for treating metabolic diseases.

scholarly journals Induction of functional uncoupling protein in guinea pigs infused with noradrenaline. Studies with isolated brown adipocytes

1987 ◽  
Vol 245 (2) ◽  
pp. 485-491 ◽  
Author(s):  
S A Cunningham ◽  
D G Nicholls
Keyword(s):  
Fatty Acid ◽  
Continuous Infusion ◽  
Guinea Pigs ◽  
Cold Adaptation ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Brown Adipocytes ◽  
Beta Agonists ◽  
Chronic Infusion ◽  
Isolated Adipocytes

Continuous infusion of noradrenaline over the interscapular brown fat of guinea pigs maintained at thermoneutrality (28-32 degrees C) induces changes similar to those after cold-adaptation. (1) Multilocular fat droplets appear within the brown adipocytes. (2) The number of mitochondria per adipocyte and the total number of adipocytes both increase. (3) Noradrenaline addition to isolated adipocytes causes near maximal uncontrolled respiration. (4) The cells become more sensitive to fatty acid-induced uncoupling. (5) The tissue-specific uncoupling protein per mg of mitochondrial protein is increased 5-fold. Specific alpha- and beta-agonists were also chronically infused. (6) Separate infusion of phenylephrine or isoprenaline was not able to stimulate mitochondriogenesis or hyperplasia. (7) Adipocytes from these animals could not be uncoupled by acute noradrenaline. (8) Simultaneous chronic infusion of phenylephrine and isoprenaline reproduced the effects of chronic noradrenaline infusion.

scholarly journals Postnatal selective suppression of lipoprotein lipase gene expression in brown adipose tissue (relative to the expression of the gene for the uncoupling protein) is not due to adrenergic insensitivity: a possible specific inhibitory effect of colostrum

1996 ◽  
Vol 314 (1) ◽  
pp. 261-267 ◽  
Author(s):  
María-Jesus OBREGÓN ◽  
Barbara CANNON ◽  
Jan NEDERGAARD
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Selective Suppression ◽  
Brown Adipose ◽  
Adrenergic Antagonist ◽  
Lpl Gene

The levels of mRNA coding for the uncoupling protein (UCP) and for lipoprotein lipase (LPL) were monitored in the brown adipose tissue of newborn rat pups. At 5 h after birth, the mRNA levels of UCP and LPL were high in pups exposed singly to 28 °C and low in pups kept singly at thermoneutrality (36 °C); in pups staying with the dam, the UCP mRNA levels were intermediate. However, the LPL mRNA levels were lower in pups staying with the dam than in pups at 36 °C, implying that factors additional to environmental temperature influenced LPL gene expression. Injection of noradrenaline into pups at thermoneutrality (36 °C) led to increases in UCP and LPL gene expression, but noradrenaline injections had no further effect in cold-exposed pups. The adrenergic effects were mediated via β-adrenergic receptors. The cold-induced increases in both UCP and LPL gene expression were abolished by the β-adrenergic antagonist propranolol. Thus differences in adrenergic responsiveness could not explain the differential expression of the UCP and LPL genes observed in pups staying with the dam. The presence of a physiological suppressor was examined by feeding single pups at 28 °C with different foods: nothing, water, Intralipid, cow's milk, rat milk and rat colostrum. None of these agents led to suppression of UCP gene expression, but colostrum led to a selective suppression of LPL gene expression. It was concluded that the genes for UCP and LPL were responsive to adrenergic stimuli immediately after birth, and it is suggested that a component of rat colostrum can selectively suppress LPL gene expression.

scholarly journals Melanocortin crosstalk with adipose functions: ACTH directly induces insulin resistance, promotes a pro-inflammatory adipokine profile and stimulates UCP-1 in adipocytes

2007 ◽  
Vol 196 (3) ◽  
pp. 465-472 ◽  
Author(s):  
K Alexander H Iwen ◽  
Oezge Senyaman ◽  
Arne Schwartz ◽  
Maren Drenckhan ◽  
Britta Meier ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Uncoupling Protein ◽  
Mitogen Activated Protein Kinase ◽  
Stress Axis ◽  
Mrna Levels ◽  
Acth Stimulation ◽  
Brown Adipocytes ◽  
The Metabolic Syndrome ◽  
Acth Treatment

The melanocortin (MC) system is a pivotal component of the hypothalamo-pituitary–adrenal (HPA) stress axis and plays an important role in the pathogenesis of obesity and the metabolic syndrome. Adipose dysfunction is implicated in the pathogenesis of these disorders. We investigated direct ACTH effects on adipose functions in immortalised murine white and brown adipocytes. MC receptor types 2 and 5 were expressed at the mRNA and protein levels and were strongly up-regulated during differentiation. Chronic ACTH stimulation did not affect adipogenesis. Insulin-induced glucose uptake in white adipocytes was acutely and transiently reduced by 45% upon ACTH treatment. Visfatin and adiponectin gene expression was reduced by about 50% in response to ACTH, while interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were acutely up-regulated by 2100 and 60% respectively. Moreover, IL-6 secretion was increased by 1450% within 4 h of ACTH treatment. In brown adipocytes, stimulation with ACTH caused a 690% increase in uncoupling protein (UCP)-1 mRNA levels within 8 h, followed by a 470% increase in UCP-1 protein concentrations after 24 h. Consistently, p38 mitogen-activated protein kinase (MAPK) phosphorylation was acutely increased by 1800% in response to ACTH stimulation, and selective inhibition of p38 MAPK abolished the ACTH-mediated UCP-1 protein increase. Taken together, ACTH acutely promotes an insulin-resistant, pro-inflammatory state and transiently enhances energy combustion. In conditions characterised by a dysregulation of the HPA stress axis such as the metabolic syndrome, direct MC interaction with adipocytes may contribute to dysregulated energy balance, insulin resistance and cardiometabolic complications.

scholarly journals Dietary curcumin supplement promotes browning and energy expenditure in postnatal overfed rats

2020 ◽  
Author(s):  
Xiaolei Zhu ◽  
Susu Du ◽  
Qinhui Yan ◽  
Cuiting Min ◽  
Nan Zhou ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Blood Lipid ◽  
Standard Diet ◽  
Mrna Levels ◽  
Lower Body Weight ◽  
Normal Feeding

Abstract Background: Early postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following with white adipose tissue (WAT) gain throughout life. This research was to investigate whether curcumin (CUR) supplement could promote WAT browning and activate thermogenesis in postnatal overfed rats.Methods and results: This study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), the SL rats were fed with a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplement had lower body weight and less WAT gain, had increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, increased respiratory exchange ratio (RER) and heat generation were consistent with expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not of the SL1% CUR rats. In addition, 2% CUR dietary supplement enhanced the serum norepinephrine (NE) levels in SL rats, with the upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT.Conclusion: Dietary CUR supplement attenuates body weight gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplement.

scholarly journals Dietary curcumin supplementation promotes browning and energy expenditure in postnatal overfed rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaolei Zhu ◽  
Susu Du ◽  
Qinhui Yan ◽  
Cuiting Min ◽  
Nan Zhou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Uncoupling Protein ◽  
Blood Lipid ◽  
Standard Diet ◽  
Mrna Levels ◽  
Lower Body Weight ◽  
Metabolic Imprinting ◽  
Normal Feeding ◽  
Subcutaneous Adipose

Abstract Background Early postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following white adipose tissue (WAT) gain throughout life. This research investigated whether curcumin (CUR) supplementation could promote WAT browning and activate thermogenesis in postnatal overfed rats. Methods and results This study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), SL rats were fed a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplementation had lower body weight and less WAT gain and had an increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, the increased heat generation were consistent with the expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not in the SL1% CUR rats. In addition, 2% CUR dietary supplementation enhanced the serum norepinephrine levels in SL rats, with upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT. Conclusion Dietary CUR supplementation attenuates body fat gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplementation.

Sign in / Sign up

Export Citation Format

Share Document