Ablation of uncoupling protein 1 causes opposing changes of glucose uptake in brown and brite fat compatible with regulation of Glut 4 gene expression

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Martin Klingenspor ◽  
Tobias Fromme ◽  
Stefanie Maurer
Keyword(s):  
Gene Expression ◽  
Glucose Uptake ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1 ◽  
Glut 4

Evidence of Browning of White Adipocytes in Poorly Survived Fat Grafts in Patients

2021 ◽  
Author(s):  
Tong Liu ◽  
Su Fu ◽  
Qian Wang ◽  
Hao Cheng ◽  
Dali Mu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uncoupling Protein ◽  
Fold Increase ◽  
Fat Grafting ◽  
Electronic Microscopy ◽  
Uncoupling Protein 1 ◽  
Fat Transfer ◽  
Flap Transfer ◽  
Fat Grafts ◽  
White Adipocytes

Abstract Background Browning adipocytes induced by burn and cancer were assumed less viable and more prone to necrosis for their hypermetabolic properties. Recent studies have shown browning of white adipose after fat engraftment in mice. Objectives We tend to evaluate whether fat transfer could induce browning biogenesis in fat grafts in humans and if it is associated with graft necrosis. Methods Necrotic adipose grafts were excised from 11 patients diagnosed with fat necrosis after fat grafting or flap transfer. Non-necrotic fat grafts were from 5 patients undergoing revisionary surgeries after flap transfer. Histology and electronic microscopy, protein and gene expression of browning related marker analyses were performed. Results Fat grafts with necrosis demonstrated a higher gene expression level of uncoupling protein-1 (>5-fold increase, **p<0.01), a master beige adipocyte marker, than non-necrotic fat grafts. Electronic microscopy and histology showed that browning adipocytes were presented in necrotic adipose in patients. Conclusions Fat transfer induced browning adipocytes in patients and was evident in patients with post grafting necrosis.

Opposite Effects of Voluntary Physical Exercise on β3-Adrenergic Receptors in the White and Brown Adipose Tissue

2019 ◽  
Vol 51 (09) ◽  
pp. 608-617 ◽  
Author(s):  
Lucia Balagova ◽  
Jan Graban ◽  
Agnesa Puhova ◽  
Daniela Jezova
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Uncoupling Protein ◽  
Control Diet ◽  
Tryptophan Depletion ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Exercise Induced

AbstractCatecholamine effects via β3-adrenergic receptors are important for the metabolism of the adipose tissue. Physical exercise is a core component of antiobesity regimens. We have tested the hypothesis that voluntary wheel running results in enhancement of β3-adrenergic receptor gene expression in the white and brown adipose tissues. The secondary hypothesis is that dietary tryptophan depletion modifies metabolic effects of exercise. Male Sprague-Dawley rats were assigned for sedentary and exercise groups with free access to running wheels for 3 weeks. All animals received normal control diet for 7 days. Both groups were fed either by low tryptophan (0.04%) diet or by control diet (0.2%) for next 2 weeks. The β3-adrenergic receptor mRNA levels in response to running increased in the retroperitoneal and epididymal fat pads. The gene expression of uncoupling protein-1 (UCP-1) was increased in the brown, while unchanged in the white fat tissues. Unlike control animals, the rats fed by low tryptophan diet did not exhibit a reduction of the white adipose tissue mass. Tryptophan depletion resulted in enhanced concentrations of plasma aldosterone and corticosterone, but had no influence on exercise-induced adrenal hypertrophy. No changes in β3-adrenergic receptor and cell proliferation measured by 5-bromo-2′-deoxyuridine incorporation in left heart ventricle were observed. The reduced β3-adrenergic receptor but not enhanced uncoupling protein-1 gene expression supports the hypothesis on hypoactive brown adipose tissue during exercise. Reduction in dietary tryptophan had no major influence on the exercise-induced changes in the metabolic parameters measured.

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

scholarly journals Alterations in Glucose Metabolism During the Transition to Heart Failure: The Contribution of UCP-2

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 552 ◽  
Author(s):  
Hanna Sarah Kutsche ◽  
Rolf Schreckenberg ◽  
Martin Weber ◽  
Christine Hirschhäuser ◽  
Susanne Rohrbach ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Contractile Function ◽  
Uncoupling Protein ◽  
Left Ventricular ◽  
Mitochondrial Uncoupling ◽  
Glut 4

The cardiac expression of the mitochondrial uncoupling protein (UCP)-2 is increased in patients with heart failure. However, the underlying causes as well as the possible consequences of these alterations during the transition from hypertrophy to heart failure are still unclear. To investigate the role of UCP-2 mechanistically, expression of UCP-2 was silenced by small interfering RNA in adult rat ventricular cardiomyocytes. We demonstrate that a downregulation of UCP-2 by siRNA in cardiomyocytes preserves contractile function in the presence of angiotensin II. Furthermore, silencing of UCP-2 was associated with an upregulation of glucose transporter type (Glut)-4, increased glucose uptake, and reduced intracellular lactate levels, indicating improvement of the oxidative glucose metabolism. To study this adaptation in vivo, spontaneously hypertensive rats served as a model for cardiac hypertrophy due to pressure overload. During compensatory hypertrophy, we found low UCP-2 levels with an upregulation of Glut-4, while the decompensatory state with impaired function was associated with an increase of UCP-2 and reduced Glut-4 expression. By blocking the aldosterone receptor with spironolactone, both cardiac function as well as UCP-2 and Glut-4 expression levels of the compensated phase could be preserved. Furthermore, we were able to confirm this by left ventricular (LV) biopsies of patients with end-stage heart failure. The results of this study show that UCP-2 seems to impact the cardiac glucose metabolism during the transition from hypertrophy to failure by affecting glucose uptake through Glut-4. We suggest that the failing heart could benefit from low UCP-2 levels by improving the efficiency of glucose oxidation. For this reason, UCP-2 inhibition might be a promising therapeutic strategy to prevent the development of heart failure.

Uncoupling protein 1 expression in murine skeletal muscle increases AMPK activation, glucose turnover, and insulin sensitivity in vivo

2008 ◽  
Vol 33 (3) ◽  
pp. 333-340 ◽  
Author(s):  
Susanne Neschen ◽  
Yvonne Katterle ◽  
Julia Richter ◽  
Robert Augustin ◽  
Stephan Scherneck ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Phosphorylation ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Uncoupling Protein ◽  
Glucose Turnover ◽  
Ampk Activation ◽  
Uncoupling Protein 1 ◽  
Uncoupling Of Oxidative Phosphorylation

Uncoupling of oxidative phosphorylation represents a potential target for the treatment of hyperglycemia and insulin resistance in obesity and type 2 diabetes. The present study investigated whether the expression of uncoupling protein 1 in skeletal muscles of transgenic (mUCP1 TG) mice modulates insulin action in major insulin target tissues in vivo. Euglycemic-hyperinsulinemic clamps (17 pM·kg lean body mass−1·min−1) were performed in 9-mo-old hemizygous male mUCP1 TG mice and wild-type (WT) littermates matched for body composition. mUCP1 TG mice exhibited fasting hypoglycemia and hypoinsulinemia compared with WT mice, whereas fasting hepatic glucose production rates were comparable in both genotypes. mUCP1 TG mice were markedly more sensitive to insulin action compared with WT mice and displayed threefold higher glucose infusion rates, enhanced skeletal muscle and white adipose tissue glucose uptake, and whole body glycolysis rates. In the absence of alterations in plasma adiponectin concentrations, acceleration of insulin-stimulated glucose turnover in skeletal muscle of mUCP1 TG mice was accompanied by increased phosphorylated Akt-to-Akt and phosphorylated AMP-activated protein kinase (AMPK)-to-AMPK ratios compared with WT mice. UCP1-mediated uncoupling of oxidative phosphorylation in skeletal muscle was paralleled by AMPK activation and thereby stimulated insulin-mediated glucose uptake in skeletal muscle.

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 Adipocyte Browning and Higher Mitochondrial Function in Periadrenal But Not SC Fat in Pheochromocytoma

2016 ◽  
Vol 101 (11) ◽  
pp. 4440-4448 ◽  
Author(s):  
Laurent Vergnes ◽  
Graeme R. Davies ◽  
Jason Y. Lin ◽  
Michael W. Yeh ◽  
Masha J. Livhits ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uncoupling Protein ◽  
Plasma Catecholamines ◽  
Global Gene Expression ◽  
University Hospital ◽  
Adrenal Tumors ◽  
Mitochondrial Activity ◽  
Adrenergic Stimulation ◽  
Uncoupling Protein 1 ◽  
Fat Depots

Context: Patients with pheochromocytoma (pheo) show presence of multilocular adipocytes that express uncoupling protein 1 within periadrenal (pADR) and omental (OME) fat depots. It has been hypothesized that this is due to adrenergic stimulation by catecholamines produced by the pheo tumors. Objective: To characterize the prevalence and respiratory activity of brown-like adipocytes within pADR, OME, and SC fat depots in human adult pheo patients. Design: This was an observational cohort study. Setting: The study took place in a university hospital. Patients: We studied 46 patients who underwent surgery for benign adrenal tumors (21 pheos and 25 controls with adrenocortical adenomas). Main outcome measure: We characterized adipocyte browning in pADR, SC, and OME fat depots for histological and immunohistological features, mitochondrial respiration rate, and gene expression. We also determined circulating levels of catecholamines and other browning-related hormones. Results: Eleven of 21 pheo pADR adipose samples, but only one of 25 pADR samples from control patients exhibited multilocular adipocytes. The pADR browning phenotype was associated with higher plasma catecholamines and raised uncoupling protein 1. Mitochondria from multilocular pADR fat of pheo patients exhibited increased rates of coupled and uncoupled respiration. Global gene expression analysis in pADR fat revealed enrichment in β-oxidation genes in pheo patients with multilocular adipocytes. No SC or OME fat depots exhibited aspects of browning. Conclusion: Browning of the pADR depot occurred in half of pheo patients and was associated with increased catecholamines and mitochondrial activity. No browning was detected in other fat depots, suggesting that other factors are required to promote browning in these depots.

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