scholarly journals Thyroid Hormone Induces Ca2+-Mediated Mitochondrial Activation in Brown Adipocytes

2021 ◽  
Vol 22 (16) ◽  
pp. 8640
Author(s):  
Minh-Hanh Thi Nguyen ◽  
Dat Da Ly ◽  
Nhung Thi Nguyen ◽  
Xu-Feng Qi ◽  
Hyon-Seung Yi ◽  
...  
Keyword(s):  
Mtor Inhibitor ◽  
Uncoupling Protein ◽  
Wide Spectrum ◽  
Mammalian Target Of Rapamycin ◽  
Uncoupling Protein 1 ◽  
Short Term ◽  
Brown Adipocytes ◽  
Short Term Exposure ◽  
Consumption Rates ◽  
Autophagic Degradation

Thyroid hormones, including 3,5,3′-triiodothyronine (T3), cause a wide spectrum of genomic effects on cellular metabolism and bioenergetic regulation in various tissues. The non-genomic actions of T3 have been reported but are not yet completely understood. Acute T3 treatment significantly enhanced basal, maximal, ATP-linked, and proton-leak oxygen consumption rates (OCRs) of primary differentiated mouse brown adipocytes accompanied with increased protein abundances of uncoupling protein 1 (UCP1) and mitochondrial Ca2+ uniporter (MCU). T3 treatment depolarized the resting mitochondrial membrane potential (Ψm) but augmented oligomycin-induced hyperpolarization in brown adipocytes. Protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were activated by T3, leading to the inhibition of autophagic degradation. Rapamycin, as an mTOR inhibitor, blocked T3-induced autophagic suppression and UCP1 upregulation. T3 increases intracellular Ca2+ concentration ([Ca2+]i) in brown adipocytes. Most of the T3 effects, including mTOR activation, UCP1 upregulation, and OCR increase, were abrogated by intracellular Ca2+ chelation with BAPTA-AM. Calmodulin inhibition with W7 or knockdown of MCU dampened T3-induced mitochondrial activation. Furthermore, edelfosine, a phospholipase C (PLC) inhibitor, prevented T3 from acting on [Ca2+]i, UCP1 abundance, Ψm, and OCR. We suggest that short-term exposure of T3 induces UCP1 upregulation and mitochondrial activation due to PLC-mediated [Ca2+]i elevation in brown adipocytes.

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 Rheb promotes brown fat thermogenesis by Notch-dependent activation of the PKA signaling pathway

2019 ◽  
Vol 11 (9) ◽  
pp. 781-790 ◽  
Author(s):  
Wen Meng ◽  
Xiuci Liang ◽  
Ting Xiao ◽  
Jing Wang ◽  
Jie Wen ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Regulatory Subunit ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Beige Fat

Abstract Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits. However, the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated. We recently found that fat-specific knockout of Rheb promoted beige fat thermogenesis. In the current study, we show that Rheb has distinct effects on thermogenic gene expression in brown and beige fat. Fat-specific knockout of Rheb decreased protein kinase A (PKA) activity and thermogenic gene expression in brown adipose tissue of high-fat diet-fed mice. On the other hand, overexpression of Rheb activated PKA and increased uncoupling protein 1 expression in brown adipocytes. Mechanistically, Rheb overexpression in brown adipocytes increased Notch expression, leading to disassociation of the regulatory subunit from the catalytic subunit of PKA and subsequent PKA activation. Our study demonstrates that Rheb, by selectively modulating thermogenic gene expression in brown and beige adipose tissues, plays an important role in regulating energy homeostasis.

scholarly journals Synergism between cAMP and PPARγSignalling in the Initiation of UCP1 Gene Expression in HIB1B Brown Adipocytes

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
H. Y. Chen ◽  
Q. Liu ◽  
A. M. Salter ◽  
M. A. Lomax
Keyword(s):  
Tandem Repeats ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Specific Gene ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Promoter Construct ◽  
Ucp1 Expression ◽  
Signalling Systems ◽  
Antagonist Gw9662

Expression of the brown adipocyte-specific gene, uncoupling protein 1 (UCP1), is increased by both PPARγstimulation and cAMP activation through their ability to stimulate the expression of the PPAR coactivator PGC1α. In HIB1B brown preadipocytes, combination of the PPARγagonist, rosiglitazone, and the cAMP stimulator forskolin synergistically increased UCP1 mRNA expression, but PGC1αexpression was only increased additively by the two drugs. The PPARγantagonist, GW9662, and the PKA inhibitor, H89, both inhibited UCP1 expression stimulated by rosiglitazone and forskolin but PGC1αexpression was not altered to the same extent. Reporter studies demonstrated that combined rosiglitazone and forskolin synergistically activated transcription from a full length 3.1 kbp UCP1 luciferase promoter construct, but the response was only additive and much reduced when a minimal 260 bp proximal UCP1 promoter was examined. Rosiglitazone and forskolin in combination were able to synergistically stimulate promoters comprising of tandem repeats of either PPREs or CREs. We conclude that rosiglitazone and forskolin act together to synergistically activate the UCP1 promoter directly rather than by increasing PGC1αexpression and by a mechanism involving cross-talk between the signalling systems regulating the CRE and PPRE on the promoters.

scholarly journals β-Adrenoceptors, but not α-adrenoceptors, stimulate AMP-activated protein kinase in brown adipocytes independently of uncoupling protein-1

Diabetologia ◽  
2005 ◽  
Vol 48 (11) ◽  
pp. 2386-2395 ◽  
Author(s):  
D. S. Hutchinson ◽  
E. Chernogubova ◽  
O. S. Dallner ◽  
B. Cannon ◽  
T. Bengtsson
Keyword(s):  
Protein Kinase ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Amp Activated Protein Kinase

scholarly journals Brown adipocytes prevent kidney stone formation via heat-producing protein, uncoupling protein 1

2020 ◽  
Vol 19 ◽  
pp. e436-e437
Author(s):  
T. Sugino ◽  
A. Okada ◽  
R. Chaya ◽  
Y. Tanaka ◽  
R. Unno ◽  
...  
Keyword(s):  
Kidney Stone ◽  
Uncoupling Protein ◽  
Stone Formation ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Kidney Stone Formation

Uncoupling protein 1 expression and high-fat diets

2011 ◽  
Vol 300 (1) ◽  
pp. R1-R8 ◽  
Author(s):  
Tobias Fromme ◽  
Martin Klingenspor
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Caloric Intake ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Thermoregulatory Function

Uncoupling protein 1 (Ucp1) is the key component of β-adrenergically controlled nonshivering thermogenesis in brown adipocytes. This process combusts stored and nutrient energy as heat. Cold exposure not only activates Ucp1-mediated thermogenesis to maintain normothermia but also results in adaptive thermogenesis, i.e., the recruitment of thermogenic capacity in brown adipose tissue. As a hallmark of adaptive thermogenesis, Ucp1 synthesis is increased proportionally to temperature and duration of exposure. Beyond this classical thermoregulatory function, it has been suggested that Ucp1-mediated thermogenesis can also be employed for metabolic thermogenesis to prevent the development of obesity. Accordingly, in times of excess caloric intake, one may expect a positive regulation of Ucp1. The general impression from an overview of the present literature is, indeed, an increased brown adipose tissue Ucp1 mRNA and protein content after feeding a high-fat diet (HFD) to mice and rats. The reported increases are very variable in magnitude, and the effect size seems to be independent of dietary fat content and duration of the feeding trial. In white adipose tissue depots Ucp1 mRNA is generally downregulated by HFD, indicating a decline in the number of interspersed brown adipocytes.

scholarly journals Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway

2021 ◽  
Vol 10 (19) ◽  
pp. 4362
Author(s):  
Ronald Peek ◽  
Lotte L. Eijkenboom ◽  
Didi D. M. Braat ◽  
Catharina C. M. Beerendonk
Keyword(s):  
Signaling Pathway ◽  
Ex Vivo ◽  
Ovarian Tissue ◽  
Autologous Transplantation ◽  
Mammalian Target Of Rapamycin ◽  
Short Term ◽  
Ovarian Cortex ◽  
Short Term Exposure ◽  
Mtorc1 Signaling ◽  
Restoration Of Fertility

Restoration of fertility by autologous transplantation of ovarian cortex tissue in former cancer patients may lead to the reintroduction of malignancy via the graft. Pharmacological ex vivo purging of ovarian cortex fragments prior to autotransplantation may reduce the risk of reseeding the cancer. In this study we have investigated the capacity of Everolimus (EVE), an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, to eradicate Ewing’s sarcoma (ES) from ovarian tissue by a short-term ex vivo treatment. Exposure of experimentally induced ES tumor foci in ovarian tissue to EVE for 24 h completely eliminated the malignant cells without detrimental effects on follicle morphology, survival or early folliculogenesis. This indicates that effective purging of ovarian cortex tissue from contaminating ES tumor foci is possible by short-term exposure to EVE.

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