scholarly journals Substrate fluxes in brown adipocytes upon adrenergic stimulation and uncoupling protein 1 ablation

2018 ◽  
Vol 1 (6) ◽  
pp. e201800136 ◽  
Author(s):  
Sabine Schweizer ◽  
Josef Oeckl ◽  
Martin Klingenspor ◽  
Tobias Fromme
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Uncoupling Protein ◽  
Adrenergic Stimulation ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Acute Response ◽  
Metabolic Adaptations ◽  
Futile Cycling ◽  
Shivering Thermogenesis

Brown adipocytes are highly specialized cells with the unique metabolic ability to dissipate chemical energy in the form of heat. We determined and inferred the flux of a number of key catabolic metabolites, their changes in response to adrenergic stimulation, and the dependency on the presence of the thermogenic uncoupling protein 1 and/or oxidative phosphorylation. This study provides reference values to approximate flux rates from a limited set of measured parameters in the future and thereby allows to evaluate the plausibility of claims about the capacity of metabolic adaptations or manipulations. From the resulting model, we delineate that in brown adipocytes (1) free fatty acids are a significant contributor to extracellular acidification, (2) glycogen is the dominant glycolytic substrate source in the acute response to an adrenergic stimulus, and (3) the futile cycling of free fatty acids between lipolysis and re-esterification into triglyceride provides a mechanism for uncoupling protein 1–independent, non-shivering thermogenesis in brown adipocytes.

Control of proteolysis by norepinephrine and insulin in brown adipocytes: role of ATP, phosphatidylinositol 3-kinase, and p70 S6K

2002 ◽  
Vol 80 (6) ◽  
pp. 541-552 ◽  
Author(s):  
Bita Moazed ◽  
M Desautels
Keyword(s):  
Fatty Acids ◽  
Protein Degradation ◽  
Kinase Activity ◽  
Uncoupling Protein ◽  
Inhibitory Effect ◽  
Phosphatidylinositol 3 Kinase ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Differentiated Cells ◽  
P70 S6k

The objective of this study was to evaluate some of the mechanisms by which norepinephrine (NE) and insulin may influence protein degradation in mouse brown adipocytes differentiated in cultures. The effects of NE and insulin, alone or in combination, on three factors known to influence proteolysis (maintenance of cell ATP and 1-phosphatidylinositol 3-kinase (PI 3-kinase) and p70 ribosomal S6-kinase (p70 S6K) activities) were examined. It was proposed that NE affects proteolysis indirectly by decreasing cell ATP from activation of uncoupling protein-1 (UCP1)-dependent mitochondrial respiration. This was tested by comparing the effects of NE and fatty acids (which directly activate UCP1) on proteolysis in brown adipocytes, as well as in pre-adipocytes and 3T3-L1 adipocytes, which do not express UCP1. An inhibitory effect of insulin on proteolysis is observed in both pre-adipocytes and differentiated cells, whereas NE and exogenously added fatty acids inhibit proteolysis only in brown adipocytes. There is a linear relationship between reductions in cell ATP and proteolysis in response to increasing concentrations of NE or fatty acids. PI 3-kinase activity is required for proteolysis, because two selective inhibitors (wortmannin and LY294002) reduce proteolysis in both pre-adipocytes and differentiated cells. This effect is not additive to that of NE, which suggests they affect the same proteolytic pathway. In contrast to NE, insulin increases PI 3-kinase activity and phosphorylation of p70 S6K. Rapamycin, which prevented insulin-dependent increase in phosphorylation of p70 S6K, increases proteolysis in brown adipocytes and antagonizes the inhibitory effect of insulin on proteolysis, but not the inhibitory effect of NE. Thus, insulin inhibits proteolysis via rapamycin-sensitive activation of p70 S6K, whereas the effect of NE appears largely to be a function of decreasing cell ATP content.Key words: brown fat, 3T3-L1 adipocytes, protein degradation, ATP, uncoupling protein-1, fatty acids, rapamycin, wortmannin, LY294002.

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.

Evaluation of Glucose Uptake and Uncoupling Protein 1 Activity in Adipose Tissue of Diabetic Mice upon β-Adrenergic Stimulation

2018 ◽  
Vol 21 (2) ◽  
pp. 249-256 ◽  
Author(s):  
Narumi Kubo ◽  
Mio Kawahara ◽  
Yuko Okamatsu-Ogura ◽  
Yosuke Miyazaki ◽  
Ryuto Otsuka ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Uncoupling Protein ◽  
Diabetic Mice ◽  
Adrenergic Stimulation ◽  
Uncoupling Protein 1

Somatostatin Modulation of Pancreatic Glucagon, Insulin, Glucose and Free Fatty Acids Following Beta-Adrenergic Stimulation

1977 ◽  
Vol 44 (6) ◽  
pp. 1088-1093 ◽  
Author(s):  
S. RAPTIS ◽  
F. ESCOBAR-JIMENEZ ◽  
J. ROSENTHAL ◽  
H. H. DITSCHUNEIT ◽  
E. F. PFEIFFER
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Pancreatic Glucagon

scholarly journals Free fatty acids regulate the uncoupling protein and alternative oxidase activities in plant mitochondria

FEBS Letters ◽  
1998 ◽  
Vol 433 (3) ◽  
pp. 237-240 ◽  
Author(s):  
Francis E. Sluse ◽  
Andréa M. Almeida ◽  
Wieslawa Jarmuszkiewicz ◽  
Anibal E. Vercesi
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Alternative Oxidase ◽  
Uncoupling Protein ◽  
Plant Mitochondria

scholarly journals Fatty Acids Rescue the Thermogenic Function of Sympathetically Denervated Brown Fat

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1428
Author(s):  
Qiang Cao ◽  
Shirong Wang ◽  
Huan Wang ◽  
Xin Cui ◽  
Jia Jing ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Temperature ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Sympathetic Innervation ◽  
Brown Fat ◽  
Key Factors ◽  
Uncoupling Protein 1 ◽  
Physiological Factors ◽  
Brown Adipose

Sympathetic nervous system (SNS) innervation into brown adipose tissue (BAT) has been viewed as an impetus for brown fat thermogenesis. However, we surprisingly discovered that BAT SNS innervation is dispensable for mice to maintain proper body temperature during a prolonged cold exposure. Here we aimed to uncover the physiological factors compensating for maintaining brown fat thermogenesis in the absence of BAT innervation. After an initial decline of body temperature during cold exposure, mice with SNS surgical denervation in interscapular BAT gradually recovered their temperature comparable to that of sham-operated mice. The surgically denervated BAT also maintained a sizable uncoupling protein 1 (UCP1) protein along with basal norepinephrine (NE) at a similar level to that of sham controls, which were associated with increased circulating NE. Furthermore, the denervated mice exhibited increased free fatty acid levels in circulation. Indeed, surgical denervation of mice with CGI-58 deletion in adipocytes, a model lacking lipolytic capacity to release fatty acids from WAT, dramatically reduced BAT UCP1 protein and rendered the mice susceptible to cold. We conclude that circulating fatty acids and NE may serve as key factors for maintaining BAT thermogenic function and body temperature in the absence of BAT sympathetic innervation.

scholarly journals Mutation yellow in agouti loci prevents age-related increase of skeletal muscle genes regulating free fatty acids oxidation

2018 ◽  
Vol 22 (2) ◽  
pp. 265-272 ◽  
Author(s):  
Y. V. Piskunova ◽  
A. Y. Kazantceva ◽  
A. V. Baklanov ◽  
N. M. Bazhan
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Free Fatty Acids ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Age Related ◽  
Brown Adipose ◽  
Ay Mice

The lethal yellow mutation in agouti loci (Ay mutation) reduces the activity of melanocortin (MC) receptors and causes hyperphagia, obesity and type two diabetes mellitus in aging mice (Ay mice). It is unknown if changes in distinct elements of the metabolic system such as white adipose tissue (WAT) and brown adipose tissue (BAT), and skeletal muscle will manifest before the development of obesity. The aim of this work was to measure the relative gene expression of key proteins that regulate carbohydrate-lipid metabolism in WAT, BAT and skeletal muscle in Ay mice before the development of obesity. C57Bl/6J mice bearing a dominant autosomal mutation Ay (Ay /a mice) and mice of the standard genotype (a/a mice, control) have been studied in three age groups: 10, 15 and 30 weeks. The relative mRNA level of genes was measured by real-time PCR in skeletal muscles (uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) (free fatty acids oxidation), solute carrier family 2 (facilitated glucose transporter), member 4 (Slc2a4) (glucose uptake)), in WAT lipoprotein lipase (Lpl) (triglyceride deposition), hormone-sensitive lipase (Lipe) (lipid mobilization), and Slc2a4 (glucose uptake)), and in BAT: uncoupling protein 1 (Ucp1) (energy expenditure). The expression of Cpt1b was reduced in young Ay mice (10 weeks), there was no transient peak of transcription of Cpt1b, Ucp3 in skeletal muscle tissue and Lipe, Slc2a4 in WAT in early adult Ay mice (15 weeks), which was noted in а/а mice. Reduction of the transcriptional activity of the studied genes in skeletal muscle and white adipose tissue can initiate the development of melanocortin obesity in Ay mice.

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.

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