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.

Browning of White Adipocytes in Fat Grafts Associated with Higher Level of Necrosis and Type 2 Macrophages Recruitment

2021 ◽  
Author(s):  
Tong Liu ◽  
Su Fu ◽  
Qian Wang ◽  
Hao Cheng ◽  
Dali Mu ◽  
...  
Keyword(s):  
Fold Increase ◽  
Chow Diet ◽  
Sham Operation ◽  
Type I ◽  
Electronic Microscopy ◽  
Fat Transfer ◽  
Fat Grafts ◽  
Female Nude ◽  
Normal Chow

Abstract Background Induced browning adipocytes were assumed less viable and more prone to necrosis for their hypermetabolic property. Our previous study showed that browning of adipocytes was more evident in fat grafts with necrosis in humans. Objectives We aimed to estimate whether fat-transfer-induced browning biogenesis was associated with necrosis and its potential inflammation mechanisms in murine models. Methods Human subcutaneous adipose from thigh or abdomen of 5 patients via liposuction were injected in 100µl or 500µl (n=20 per group) into the dorsal flank of 6-8-week female nude mice fed with normal chow diet, and harvested after 2, 4, 8 and 12 weeks. Control groups did not receive any grafting procedures (sham operation), where lipoaspirates were analyzed immediately after harvest. Histology and electronic microscopy, immunological analyses of browning markers, necrosis marker, and type I/II macrophages markers in mice were performed. Results Histology and electronic microscopy showed browning adipocytes in in fat grafts with higher level of necrosis (0.435±0.017pg/ml for cleaved caspase-3, **p<0.01), IL-6(749.0±134.1pg/ml,***p<0.001) and infiltration of type 2 macrophage profiles in mice(2-fold increase, *p<0.05). Conclusions Browning of adipocytes induced by fat transfer in mice is in parallel with post-grafting necrotic levels, associated with elevated IL-6 and activated M2 macrophages profiles which promote browning development.

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.

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.

Photoperiodic regulation of gene expression in brown and white adipose tissue of Siberian hamsters (Phodopus sungorus)

2002 ◽  
Vol 282 (1) ◽  
pp. R114-R121 ◽  
Author(s):  
Gregory E. Demas ◽  
Robert R. Bowers ◽  
Timothy J. Bartness ◽  
Thomas W. Gettys
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Regulation Of Gene Expression ◽  
Ribonuclease Protection Assay ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Siberian Hamsters ◽  
Brown Adipose

Siberian hamsters exhibit seasonal fluctuations in white adipose tissue (WAT) mass, with peaks in long “summerlike” days (LDs) and nadirs in short “winterlike” days (SDs). These responses can be mimicked in the laboratory after transfer from LDs to SDs. The purpose of the present study was to test whether changes in WAT and brown adipose tissue (BAT) gene expression that are mediated by the sympathetic nervous system in other obesity models are also associated with seasonal adiposity changes in Siberian hamsters. SDs decreased WAT mass and leptin mRNA, increased WAT β3-adrenoceptor mRNA, and induced retroperitoneal WAT uncoupling protein-1 mRNA (the latter measured by RT-PCR, others measured by ribonuclease protection assay) while increasing BAT uncoupling protein-1 and peroxisome proliferator-activated receptor-γ coactivator-1 mRNAs. These effects were not due to SD-induced gonadal regression and largely occurred before the usual SD-induced decreases in food intake. Thus the SD-induced decreased adiposity of Siberian hamsters may be due to a coordinated suite of WAT and BAT gene transcription changes ultimately increasing lipid mobilization and utilization.

scholarly journals Differential effects of retinoic acid on uncoupling protein-1 and leptin gene expression

1998 ◽  
Vol 157 (2) ◽  
pp. 237-243 ◽  
Author(s):  
MV Kumar ◽  
PJ Scarpace
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Uncoupling Protein ◽  
Whole Body ◽  
Mrna Levels ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Cgp 12177

All-trans-retinoic acid (RA), one of the active metabolites of vitamin A, can increase the expression of uncoupling protein-1 (UCP1) gene. To determine whether RA stimulates brown adipose tissue (BAT) thermogenesis and modulates leptin gene expression in vivo, 6-month-old, vitamin-A sufficient, F344 x BN rats were administered a single dose of RA (7.5 mg/kg, i.p.) or the beta 3-adrenergic receptor (beta 3AR) specific agonist, CGP 12177 (0.75 mg/kg). Levels of UCP1 mRNA in BAT and leptin mRNA in perirenal white adipose tissue (WAT) were examined 5 h after treatment. mRNA levels of lipoprotein lipase (LPL) were also examined in BAT and perirenal WAT. Administration of CGP 12177 caused the expected increase in UCP1 mRNA levels. RA treatment also significantly increased UCP1 mRNA levels but to a lesser extent than CGP 12177. In contrast, there was no acute effect of RA on whole body oxygen consumption, one measure of BAT thermogenesis. Both CGP 12177 and RA treatment decreased levels of leptin mRNA to a similar extent. RA treatment had no effect on mRNA levels of LPL in BAT or perirenal WAT. There were no changes in total DNA content, total protein content, or in the levels of beta-actin mRNA in either BAT or perirenal WAT upon administration of RA or CGP 12177. Thus, the acute effects of RA paralleled the effects of the beta 3AR specific agonist, CGP 12177, on UCP1 and leptin gene expression. This involvement of RA in positive regulation of UCP1 mRNA and negative regulation of leptin mRNA suggests a contrasting role for RA in energy homeostasis.

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