scholarly journals Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lisa Suwandhi ◽  
Irem Altun ◽  
Ruth Karlina ◽  
Viktorian Miok ◽  
Tobias Wiedemann ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Tissue Expansion ◽  
White Adipocyte ◽  
The Metabolic Syndrome ◽  
Beige Adipocytes ◽  
Subcutaneous Adipose ◽  
Old Mice

AbstractAdipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.

scholarly journals White Adipose Tissue Expansion in Multiple Symmetric Lipomatosis Is Associated with Upregulation of CK2, AKT and ERK1/2

2020 ◽  
Vol 21 (21) ◽  
pp. 7933
Author(s):  
Marta Sanna ◽  
Christian Borgo ◽  
Chiara Compagnin ◽  
Francesca Favaretto ◽  
Vincenzo Vindigni ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Tissue Expansion ◽  
Specific Marker ◽  
Type I ◽  
Vitro Assay ◽  
Multiple Symmetric Lipomatosis ◽  
Paired Control ◽  
Subcutaneous Adipose

Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by overgrowing lipomatous tissue (LT) in the subcutaneous adipose tissue (SAT). What LT is and how it expands are not completely understood; previous data suggested that it could derive from brown AT precursors. In six MSL type I patients, we compared LT morphology by histological and immunohistochemistry (IHC) analysis, gene expression, by qPCR, kinase activity, by Western Blot and in vitro assay to paired-control SAT using AT from patients with pheochromocytoma as a human browning reference. In the stromal vascular fraction (SVF), we quantified adipose stem cells (ASCs) by flow cytometry, the proliferation rate, white and beige adipogenic potential and clonogenicity and adipogenicity by a limiting dilution assay. LT displayed white AT morphology and expression pattern and did not show increased levels of the brown-specific marker UCP1. In LT, we evidenced AKT, CK2 and ERK1/2 hyperactivation. LT-SVF contained increased ASCs, proliferated faster, sprouted clones and differentiated into adipocytes better than the control, displaying enhanced white adipogenic potential but not increased browning compared to SAT. In conclusion, LT is a white AT depot expanding by hyperplasia through increased stemness and enhanced white adipogenesis upregulating AKT, CK2 and ERK1/2, which could represent new targets to counteract MSL.

scholarly journals Long-Term Severe In Vitro Hypoxia Exposure Enhances the Vascularization Potential of Human Adipose Tissue-Derived Stromal Vascular Fraction Cell Engineered Tissues

2021 ◽  
Vol 22 (15) ◽  
pp. 7920
Author(s):  
Myroslava Mytsyk ◽  
Giulia Cerino ◽  
Gregory Reid ◽  
Laia Gili Sole ◽  
Friedrich S. Eckstein ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Therapeutic Potential ◽  
Stromal Vascular Fraction ◽  
Human Adipose Tissue ◽  
Bioreactor Culture ◽  
Proliferating Cells ◽  
Angiogenic Potential ◽  
Engineered Tissues

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

scholarly journals Lsd1 prevents age-programed loss of beige adipocytes

2017 ◽  
Vol 114 (20) ◽  
pp. 5265-5270 ◽  
Author(s):  
Delphine Duteil ◽  
Milica Tosic ◽  
Dominica Willmann ◽  
Anastasia Georgiadi ◽  
Toufike Kanouni ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Peroxisome Proliferator ◽  
Fat Cell ◽  
White Adipocyte ◽  
White Adipocytes ◽  
Age Related ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
And Function

Aging is accompanied by major changes in adipose tissue distribution and function. In particular, with time, thermogenic-competent beige adipocytes progressively gain a white adipocyte morphology. However, the mechanisms controlling the age-related transition of beige adipocytes to white adipocytes remain unclear. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser enzyme positively regulating differentiation and function of adipocytes. Here we show that Lsd1 levels decrease in aging inguinal white adipose tissue concomitantly with beige fat cell decline. Accordingly, adipocyte-specific increase of Lsd1 expression is sufficient to rescue the age-related transition of beige adipocytes to white adipocytes in vivo, whereas loss of Lsd1 precipitates it. Lsd1 maintains beige adipocytes by controlling the expression of peroxisome proliferator-activated receptor α (Ppara), and treatment with a Ppara agonist is sufficient to rescue the loss of beige adipocytes caused by Lsd1 ablation. In summary, our data provide insights into the mechanism controlling the age-related beige-to-white adipocyte transition and identify Lsd1 as a regulator of beige fat cell maintenance.

Additive effects of cortisol and growth hormone on regional and systemic lipolysis in humans

2004 ◽  
Vol 286 (3) ◽  
pp. E488-E494 ◽  
Author(s):  
C. B. Djurhuus ◽  
C. H. Gravholt ◽  
S. Nielsen ◽  
S. B. Pedersen ◽  
N. Møller ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Additive Effects ◽  
Subcutaneous Adipose ◽  
In Vivo Effects ◽  
Circulating Levels

Growth hormone (GH) and cortisol are important to ensure energy supplies during fasting and stress. In vitro experiments have raised the question whether GH and cortisol mutually potentiate lipolysis. In the present study, combined in vivo effects of GH and cortisol on adipose and muscle tissue were explored. Seven lean males were examined four times over 510 min. Microdialysis catheters were inserted in the vastus lateralis muscle and in the subcutaneous adipose tissue of the thigh and abdomen. A pancreatic-pituitary clamp was maintained with somatostatin infusion and replacement of GH, insulin, and glucagon at baseline levels. At t = 150 min, administration was performed of NaCl (I), a 2 μg·kg-1·min-1hydrocortisone infusion (II), a 200-μg bolus of GH (III), or a combination of II and III (IV). Systemic free fatty acid (FFA) turnover was estimated by [9,10-3H]palmitate appearance. Circulating levels of glucose, insulin, and glucagon were comparable in I-IV. GH levels were similar in I and II (0.50 ± 0.08 μg/l, mean ± SE). Peak levels during III and IV were ∼9 μg/l. Cortisol levels rose to ∼900 nmol/l in II and IV. Systemic (i.e., palmitate fluxes, s-FFA, s-glycerol) and regional (interstitial adipose tissue and skeletal muscle) markers of lipolysis increased in response to both II and III. In IV, they were higher and equal to the isolated additive effects of the two hormones. In conclusion, we find that GH and cortisol stimulate systemic and regional lipolysis independently and in an additive manner when coadministered. On the basis of previous studies, we speculate that the mode of action is mediated though different pathways.

scholarly journals A Cross-Machine Comparison of Shear-Wave Speed Measurements Using 2D Shear-Wave Elastography in the Normal Female Breast

2021 ◽  
Vol 11 (20) ◽  
pp. 9391
Author(s):  
Emma Harris ◽  
Ruchi Sinnatamby ◽  
Elizabeth O’Flynn ◽  
Anna M. Kirby ◽  
Jeffrey C. Bamber
Keyword(s):  
Adipose Tissue ◽  
Shear Wave ◽  
Subcutaneous Adipose Tissue ◽  
Wave Speed ◽  
Shear Wave Elastography ◽  
Shear Wave Speed ◽  
Skin Region ◽  
Subcutaneous Adipose

Quantitative measures of radiation-induced breast stiffness are required to support clinical studies of novel breast radiotherapy regimens and exploration of personalised therapy, however, variation between shear-wave elastography (SWE) machines may limit the usefulness of shear-wave speed (cs) for this purpose. Mean cs measured in four healthy volunteers’ breasts and a phantom using 2D-SWE machines Acuson S2000 (Siemens Medical Solutions) and Aixplorer (Supersonic Imagine) were compared. Shear-wave speed was measured in the skin region, subcutaneous adipose tissue and parenchyma. cs estimates were on average 2.3% greater when using the Aixplorer compared to S2000 in vitro. In vivo, cs estimates were on average 43.7%, 36.3% and 49.9% significantly greater (p << 0.01) when using the Aixplorer compared to S2000, for skin region, subcutaneous adipose tissue and parenchyma, respectively. In conclusion, despite relatively small differences between machines observed in vitro, large differences in absolute measures of shear wave speed measured were observed in vivo, which may prevent pooling of cross-machine data in clinical studies of the breast.

Production of glutamine and utilization of glutamate by rat subcutaneous adipose tissue in vivo

1994 ◽  
Vol 266 (1) ◽  
pp. E151-E154 ◽  
Author(s):  
T. J. Kowalski ◽  
M. Watford
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Sampling Technique ◽  
Calibration Method ◽  
Glutamine Metabolism ◽  
Whole Body ◽  
Arterial Blood ◽  
Subcutaneous Adipose

Information about adipose tissue amino acid metabolism is limited, with most data derived from studies in vitro. The purpose of this study was to further characterize the role of adipose tissue in glutamine metabolism in the rat in vivo. The extracellular concentrations of glutamine, glutamate, alanine, and ammonia were measured in the rat inguinal fat pad using a microdialysis sampling technique. A calibration method was used to accurately assess the extracellular levels of metabolites, and a comparison of these concentrations with those in arterial blood allowed determination of the net flux of each compound. The adipose tissue-arterial blood concentration differences were 122 +/- 19, 54 +/- 37, -61 +/- 21, and -28 +/- 13 microM for glutamine, alanine, glutamate, and ammonia, respectively, indicating a production of glutamine and an uptake of glutamate by subcutaneous adipose tissue. The magnitude of glutamine production suggests that adipose tissue may play a significant role in whole body glutamine homeostasis.

scholarly journals Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Peter Succar ◽  
Edmond J. Breen ◽  
Donald Kuah ◽  
Benjamin R. Herbert
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Disease Progression ◽  
Proinflammatory Cytokines ◽  
Mechanism Of Action ◽  
Stromal Vascular Fraction ◽  
Slow Disease Progression

Osteoarthritis (OA) can be a debilitating degenerative disease and is the most common form of arthritic disease. There is a general consensus that current nonsurgical therapies are insufficient for younger OA sufferers who are not candidates for knee arthroplasties. Adipose-derived mesenchymal stem cells (MSCs) therapy for the treatment of OA can slow disease progression and lead to neocartilage formation. The mechanism of action is secretion driven. Current clinical preparations from adipose tissue for the treatment of OA include autologous stromal vascular fraction (SVF), SVF plus mature adipocytes, and culture-purified MSCs. Herein we have combined these human adipose-derived preparations with Hyaluronan (Hylan G-F 20: Synvisc)in vitroand measured alterations in cytokine profile. SVF plus mature adipocytes showed the greatest decreased in the proinflammatory cytokines IL-1β, IFN-γ, and VEGF. MCP-1 and MIP-1αdecreased substantially in the SVF preparations but not the purified MSCs. The purified MSC preparation was the only one to show increase in MIF. Overall the SVF plus mature adipocytes preparation may be most suited of all the preparations for combination with HA for the treatment of OA, based on the alterations of heavily implicated cytokines in OA disease progression. This will require further validation usingin vivomodels.

Dehydroepiandrosterone reduces preadipocyte proliferation via androgen receptor

2012 ◽  
Vol 302 (6) ◽  
pp. E694-E704 ◽  
Author(s):  
Kei Fujioka ◽  
Kazuo Kajita ◽  
Zhiliang Wu ◽  
Takayuki Hanamoto ◽  
Takahide Ikeda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Androgen Receptor ◽  
Cell Growth ◽  
Stromal Vascular Fraction ◽  
Common Mechanism ◽  
Reduced Body ◽  
Quantification Analysis

Several studies have suggested that both testosterone and dehydroepiandrosterone (DHEA) have weight-reducing and antidiabetic effects, especially in rodent studies; however, the precise mechanism of their action remains unclear. Here, we investigated the effect of DHEA on cell growth in adipose tissue. The appearance of senescence-associated β-galactosidase in stromal vascular fraction (SVF) isolated from Otsuka Long-Evans Tokushima fatty rats, an animal model of inherent obese type 2 diabetes, was prevented by DHEA administration. Next, the effects of DHEA and testosterone were compared in vivo and in vitro to evaluate whether these hormones influence cell growth in adipose tissue. Both DHEA and testosterone reduced body weight and epididymal fat weight equivalently when administered for 4 wk. To assess the effect of DHEA and testosterone on cell growth in adipose tissue, 5-bromo-2′-deoxyuridine (BrdU) uptake by SVF was measured. Quantification analysis of BrdU uptake by examining DNA isolated from each SVF revealed that treatment with DHEA and testosterone reduced cell replication. These results indicated that DHEA- and testosterone-induced decreased adiposity was associated with reduced SVF growth. Incubation with DHEA and testosterone equally decreased BrdU uptake by 3T3-L1 preadipocytes. Pretreatment with the androgen receptor (AR) inhibitor flutamide, but not the estrogen receptor inhibitor fulvestrant, abolished these effects. Knockdown of AR with siRNA also inhibited DHEA-induced decreases in BrdU uptake. These results suggest that DHEA-induced growth suppression of preadipocytes is mediated via AR. Therefore, both DHEA and testosterone similarly decrease adipocyte growth possibly via a common mechanism.

The role and regulation of 11β-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome

2013 ◽  
Vol 15 (2) ◽  
Author(s):  
Roland H. Stimson ◽  
Brian R. Walker
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Selective Inhibition ◽  
Hydroxysteroid Dehydrogenase ◽  
The Metabolic Syndrome ◽  
Specific Regulation ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

AbstractThe cortisol regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies tissue glucocorticoid levels, particularly in the liver and adipose tissue. The importance of this enzyme in causing metabolic disease was highlighted by transgenic mice which over- or under-expressed 11β-HSD1; consequently, selective 11β-HSD1 inhibitors have been widely developed as novel agents to treat obesity and type 2 diabetes mellitus (T2DM). This review focuses on the importance of 11β-HSD1 in humans which has been more difficult to ascertain. The recent development of a deuterated cortisol tracer has allowed us to quantify in vivo cortisol production by 11β-HSD1. These results have been surprising, as cortisol production rates by 11β-HSD1 are at least equivalent to that of the adrenal glands. The vast majority of this production is by the liver (>90%) with a smaller contribution from subcutaneous adipose tissue and possibly skeletal muscle, but with no detectable production from visceral adipose tissue. This tracer has also allowed us to quantify the tissue-specific regulation of 11β-HSD1 observed in obesity and obesity-associated T2DM, determine the likely basis for this dysregulation, and identify obese patients with T2DM as the group most likely to benefit from selective inhibition of 11β-HSD1. Some of these inhibitors have now reached Phase II clinical development, demonstrating efficacy in the treatment of T2DM. We review these results and discuss whether selective 11β-HSD1 inhibitors are likely to be an important new therapy for metabolic disease.

401 MIGRATION AND THERAPEUTIC POTENTIAL OF PORCINE ADULT ADIPOSE-DERIVED MESENCHYMAL STEM CELLS

2010 ◽  
Vol 22 (1) ◽  
pp. 357 ◽  
Author(s):  
S. M. Wilson ◽  
E. Monaco ◽  
M. S. Goldwasser ◽  
S. G. Clark ◽  
W. L. Hurley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Adult Stem Cells ◽  
Bone Defects ◽  
Adipose Derived Stem Cells ◽  
Subcutaneous Adipose ◽  
Time Point

Bone marrow is one current source of adult stem cells for therapeutic purposes; however, the magnitude and accessibility of subcutaneous adipose tissue in humans make it an attractive alternative. Numerous in vitro studies have been conducted to determine how these cells act in vitro, but it is imperative to determine the vast abilities of these cells in vivo. The objective of this study was to evaluate in vivo migration and bone healing ability after transplanting adipose-derived stem cells (ADSC) in a swine model. Adipose-derived stem cells were isolated from subcutaneous adipose tissue of adult Yorkshire pigs and cultured in vitro. At 80 to 90% confluence/passage 3, the cells were trypsinized and labeled in suspension with carboxyfluorescein succinimidyl ester (CFDA-SE). This project included 20 pigs weighing between 63.5 and 81.7 kg. Bilateral mandibular osteoectomies with 10-mm defects were performed on each pig. Of the 20 pigs, half received a treatment of 2.5 million CFDA-SE labeled stem cells administered directly into each defect (DI), and the remaining half received a treatment of approximately 5 million CFDA-SE labeled stem cells through an ear vein injection via catheter (EVI). The time points were 1 h and 2 and 4 wk, with 2 pigs per time with the DI and EVI treatments. Pigs were slaughtered at each time, and spleen, liver, lung, kidney, ear vein, blood, and mandible tissues were collected. Blood samples were collected from the jugular vein with EDTA and processed via flow cytometry after collection. Tissues were fixed in 10% buffered formalin for histology. Fluorescent microscopy (CFDA-SE excitation/emission is 492/517 nm) has confirmed that transplanted ADSC do indeed migrate to a site of injury or trauma. Labeled cells were also present in blood collected from the 1-h time point group. Currently, we have not seen the presence of labeled ADSC in the other tissues (spleen, liver, lung, and kidney) after the 1-h time point. We did observe that ADSC administered by DI and EVI were able to significantly heal and regenerate bone defects within 4 wk post-surgery (P < 0.05, ANOVA with F-test), in contrast to bone defects in pigs that did not receive cell injections (control). Evidence of ADSC-related healing and bone regeneration was evident by gross visualization, dual-energy x-ray absorptiometry (DXA) and micro computer tomography (microCT) analysis. The clinical implications of these results are significant for treating many diseases in which inflammation or defects exist, such as cardiac disease, neurological disease, or traumatic injuries to both soft and hard tissue. If the adult stem cells can be harvested from fat, encouraged to produce bone or cartilage, and then reinserted into defects, treatment protocols for trauma victims could be developed that would reduce the need for alternate harvesting techniques for bone. This work was support by a grant from the Illinois Regenerative Medicine Institute (IDPH # 63080017).

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