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 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 Regulation of 11β-HSD1 expression during adipose tissue expansion by hypoxia through different activities of NF-κB and HIF-1α

2013 ◽  
Vol 304 (10) ◽  
pp. E1035-E1041 ◽  
Author(s):  
Jong Han Lee ◽  
Zhanguo Gao ◽  
Jianping Ye
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Hypoxia Inducible Factor ◽  
Tissue Expansion ◽  
Nuclear Factor Κb ◽  
Elevated Expression ◽  
Subcutaneous Adipose

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is involved in the pathogenesis of type 2 diabetes by generating active glucocorticoids (cortisol and corticosterone) that are strong inhibitors of angiogenesis. However, the mechanism of 11β-HSD1 gene expression and its relationship to adipose angiogenesis are largely unknown. To address this issue, we examined 11β-HSD1 expression in visceral and subcutaneous adipose tissue (AT) of diet-induced obese (DIO) mice during weight gain and investigated the gene regulation by hypoxia in vitro. 11β-HSD1 mRNA was reduced in the adipose tissues during weight gain in DIO mice, and the reduction was associated with an elevated expression of angiogenic factors. In vitro, 11β-HSD1 expression was induced in mRNA and protein by hypoxia. Of the two transcription factors activated by hypoxia, the nuclear factor-κB (NF-κB) enhanced but the hypoxia inducible factor-1α (HIF-1α) reduced 11β-HSD1 expression. 11β-HSD1 expression was elevated by NF-κB in epididymal fat of aP2-p65 mice. The hypoxia-induced 11β-HSD1 expression was attenuated by NF-κB inactivation in p65-deficient cells but enhanced by HIF-1 inactivation in HIF-1α-null cells. These data suggest that 11β-HSD1 expression is upregulated by NF-κB and downregulated by HIF-1α. During AT expansion in DIO mice, the reduction of 11β-HSD1 expression may reflect a dominant HIF-1α activity in the adipose tissue. This study suggests that NF-κB may mediate the inflammatory cytokine signal to upregulate 11β-HSD1 expression.

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 Derivation, characterization, and in vitro cell regeneration of canine white adipose tissue-derived mesenchymal stem cells obtained from a mesenteric region

2021 ◽  
Vol 82 (1) ◽  
Author(s):  
Anirban Mandal ◽  
Ajeet Kumar Jha ◽  
Dew Biswas ◽  
Shyamal Kanti Guha
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Cell Regeneration ◽  
Wound Healing Assay ◽  
Chain Reaction ◽  
Polymerase Chain

Abstract Background The study was conducted to assess the characterization, differentiation, and in vitro cell regeneration potential of canine mesenteric white adipose tissue-derived mesenchymal stem cells (AD-MSCs). The tissue was harvested through surgical incision and digested with collagenase to obtain a stromal vascular fraction. Mesenchymal stem cells isolated from the stromal vascular fraction were characterized through flow cytometry and reverse transcription-polymerase chain reaction. Assessment of cell viability, in vitro cell regeneration, and cell senescence were carried out through MTT assay, wound healing assay, and β-galactosidase assay, respectively. To ascertain the trilineage differentiation potential, MSCs were stained with alizarin red for osteocytes, alcian blue for chondrocytes, and oil o red for adipocytes. In addition, differentiated cells were characterized through a reverse transcription-polymerase chain reaction. Results We observed the elongated, spindle-shaped, and fibroblast-like appearance of cells after 72 h of initial culture. Flow cytometry results showed positive expression for CD44, CD90, and negative expression for CD45 surface markers. Population doubling time was found 18–24 h for up to the fourth passage and 30±0.5 h for the fifth passage. A wound-healing assay was used to determine cell migration rate which was found 136.9 ± 4.7 μm/h. We observed long-term in vitro cell proliferation resulted in MSC senescence. Furthermore, we also found that the isolated cells were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. Conclusions Mesenteric white adipose tissue was found to be a potential source for isolation, characterization, and differentiation of MSCs. This study might be helpful for resolving the problems regarding the paucity of information concerning the basic biology of stem cells. The large-scale use of AD-MSCs might be a remedial measure in regenerative medicine.

scholarly journals Divergent functions of endotrophin on different cell populations in adipose tissue

2016 ◽  
Vol 311 (6) ◽  
pp. E952-E963 ◽  
Author(s):  
Yueshui Zhao ◽  
Xue Gu ◽  
Ningyan Zhang ◽  
Mikhail G. Kolonin ◽  
Zhiqiang An ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Accumulation ◽  
Lysyl Oxidase ◽  
Stromal Vascular Fraction ◽  
Cell Types ◽  
Marker Genes ◽  
New Perspective ◽  
Collagen Genes ◽  
Different Cell Types

Endotrophin is a cleavage product of collagen 6 (Col6) in adipose tissue (AT). Previously, we demonstrated that endotrophin serves as a costimulator to trigger fibrosis and inflammation within the unhealthy AT milieu. However, how endotrophin affects lipid storage and breakdown in AT and how different cell types in AT respond to endotrophin stimulation remain unknown. In the current study, by using a doxycycline-inducible mouse model, we observed significant upregulation of adipogenic genes in the white AT (WAT) of endotrophin transgenic mice. We further showed that the mice exhibited inhibited lipolysis and accelerated hypertrophy and hyperplasia in WAT. To investigate the effects of endotrophin in vitro, we incubated different cell types from AT with conditioned medium from endotrophin-overexpressing 293T cells. We found that endotrophin activated multiple pathological pathways in different cell types. Particularly in 3T3-L1 adipocytes, endotrophin triggered a fibrotic program by upregulating collagen genes and promoted abnormal lipid accumulation by downregulating hormone-sensitive lipolysis gene and decreasing HSL phosphorylation levels. In macrophages isolated from WAT, endotrophin stimulated higher expression of the collagen-linking enzyme lysyl oxidase and M1 proinflammatory marker genes. In the stromal vascular fraction isolated from WAT, endotrophin induced upregulation of both profibrotic and proinflammatory genes. In conclusion, our study provides a new perspective on the effect of endotrophin in abnormal lipid accumulation and a mechanistic insight into the roles played by adipocytes and a variety of other cell types in AT in shaping the unhealthy microenvironment upon endotrophin treatment.

scholarly journals Release of Inflammatory Mediators by Human Adipose Tissue Is Enhanced in Obesity and Primarily by the Nonfat Cells: A Review

2010 ◽  
Vol 2010 ◽  
pp. 1-20 ◽  
Author(s):  
John N. Fain
Keyword(s):  
Adipose Tissue ◽  
In Vitro Release ◽  
Human Adipose Tissue ◽  
Fat Cells ◽  
Omental Adipose Tissue ◽  
Subcutaneous Adipose ◽  
Circulating Levels ◽  
Pai 1

This paper considers the role of putative adipokines that might be involved in the enhanced inflammatory response of human adipose tissue seen in obesity. Inflammatory adipokines [IL-6, IL-10, ACE, TGFβ1, TNFα, IL-1β, PAI-1, and IL-8] plus one anti-inflammatory [IL-10] adipokine were identified whose circulating levels as well as in vitro release by fat are enhanced in obesity and are primarily released by the nonfat cells of human adipose tissue. In contrast, the circulating levels of leptin and FABP-4 are also enhanced in obesity and they are primarily released by fat cells of human adipose tissue. The relative expression of adipokines and other proteins in human omental as compared to subcutaneous adipose tissue as well as their expression in the nonfat as compared to the fat cells of human omental adipose tissue is also reviewed. The conclusion is that the release of many inflammatory adipokines by adipose tissue is enhanced in obese humans.

scholarly journals The Mineralocorticoid Receptor Antagonist Eplerenone Suppress Interstitial Fibrosis in Subcutaneous Adipose Tissue in Type 2 Diabetes Patients

2020 ◽  
Author(s):  
Ada Admin ◽  
Marie Louise Johansen ◽  
Jaime Ibarrola ◽  
Amaya Fernández-Celis ◽  
Morten Schou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Receptor Antagonist ◽  
Subcutaneous Adipose Tissue ◽  
Mineralocorticoid Receptor ◽  
Prostaglandin D2 ◽  
Type I ◽  
Mineralocorticoid Receptor Antagonist ◽  
Subcutaneous Adipose

Activation of the mineralocorticoid receptor (MR) may promote dysfunctional adipose tissue in patients with type 2 diabetes, where increased pericellular fibrosis has emerged as a major contributor. The knowledge of the association between the MR, fibrosis and the effects of an MR antagonist (MRA) in human adipocytes remains very limited. The present sub-study including 30 participants was prespecified as part of the Mineralocorticoid Receptor Antagonist in type 2 Diabetes (MIRAD) trial, randomizing patients to either high dose eplerenone or placebo for 26 weeks. In adipose tissue biopsies, changes in fibrosis were evaluated by immunohistological examinations and by the expression of mRNA and protein markers of fibrosis. Treatment with an MRA reduced pericellular fibrosis, synthesis of the major subunits of collagen type I and VI, and the profibrotic factor α-smooth muscle actin, as compared to placebo in subcutaneous adipose tissue. Furthermore, we found decreased expression of the MR and downstream molecules neutrophil gelatinase–associated lipocalin, galectin-3, and lipocalin-like prostaglandin D2 synthase with an MRA. In conclusions, we present original data demonstrating reduced fibrosis in adipose tissue with inhibition of the MR, which could be a potential therapeutic approach to prevent the extracellular matrix remodeling of adipose tissue in type 2 diabetes.

scholarly journals Generation of immune cell containing adipose organoids for in vitro analysis of immune metabolism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jacqueline Taylor ◽  
Julia Sellin ◽  
Lars Kuerschner ◽  
Lennart Krähl ◽  
Yasmin Majlesain ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Immune Cell ◽  
Stromal Vascular Fraction ◽  
Cell Populations ◽  
Endocrine Organ ◽  
Vitro Analysis ◽  
In Vitro Analysis ◽  
Better Than

AbstractAdipose tissue is an organized endocrine organ with important metabolic and immunological functions and immune cell-adipocyte crosstalk is known to drive various disease pathologies. Suitable 3D adipose tissue organoid models often lack resident immune cell populations and therefore require the addition of immune cells isolated from other organs. We have created the first 3D adipose tissue organoid model which could contain and maintain resident immune cell populations of the stromal vascular fraction (SVF) and proved to be effective in studying adipose tissue biology in a convenient manner. Macrophage and mast cell populations were successfully confirmed within our organoid model and were maintained in culture without the addition of growth factors. We demonstrated the suitability of our model for monitoring the lipidome during adipocyte differentiation in vitro and confirmed that this model reflects the physiological lipidome better than standard 2D cultures. In addition, we applied mass spectrometry-based lipidomics to track lipidomic changes in the lipidome upon dietary and immunomodulatory interventions. We conclude that this model represents a valuable tool for immune-metabolic research.

Influence of somatotropin on lipid metabolism and IGF gene expression in porcine adipose tissue

1992 ◽  
Vol 263 (4) ◽  
pp. E637-E645 ◽  
Author(s):  
C. K. Wolverton ◽  
M. J. Azain ◽  
J. Y. Duffy ◽  
M. E. White ◽  
T. G. Ramsay
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Dietary Fat ◽  
Subcutaneous Adipose Tissue ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Systemic Factors ◽  
Subcutaneous Adipose ◽  
Acid Esterification

The present study was designed to evaluate the effects of porcine somatotropin (pST) treatment (2 mg/day) and dietary fat (10%) separately and in combination on the metabolic activity of subcutaneous adipose tissue, serum adipogenic activity, and insulin-like growth factor (IGF) gene expression within adipose tissue from growing 5- to 6-mo-old barrows. This study attempted to determine how these factors might contribute to the reported changes in adiposity of treated swine. Biopsies of adipose tissue were collected after 28 days of treatment following anesthesia with thiopental sodium (15 mg/kg iv). Somatotropin inhibited in vitro glucose oxidation and lipogenesis in adipose tissue but did not affect fatty acid esterification. Adipogenic activity of serum was not altered by pST treatment. Subcutaneous adipose tissue contained mRNA for IGF-I and -II, and pST administration increased the abundance of IGF-I mRNA. Dietary fat had no effect on these variables. Thus somatotropin reduces glucose metabolism in porcine subcutaneous adipose tissue. Preadipocyte proliferation and differentiation are not affected by somatotropin through its actions on systemic factors. Dietary fat provides no additional benefit in combination with pST administration to affect accretion of adipose tissue in growing swine.

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