scholarly journals GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity

2019 ◽  
pp. 201822067 ◽  
Author(s):  
Injae Hwang ◽  
Kyuri Jo ◽  
Kyung Cheul Shin ◽  
Jong In Kim ◽  
Yul Ji ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Epididymal Adipose Tissue ◽  
Adipose Derived Stem Cells ◽  
Tissue Macrophage ◽  
Monocyte Migration ◽  
Fat Depot ◽  
Subcutaneous Adipose

Accumulating evidence suggests that subcutaneous and visceral adipose tissues are differentially associated with metabolic disorders. In obesity, subcutaneous adipose tissue is beneficial for metabolic homeostasis because of repressed inflammation. However, the underlying mechanism remains unclear. Here, we demonstrate that γ-aminobutyric acid (GABA) sensitivity is crucial in determining fat depot-selective adipose tissue macrophage (ATM) infiltration in obesity. In diet-induced obesity, GABA reduced monocyte migration in subcutaneous inguinal adipose tissue (IAT), but not in visceral epididymal adipose tissue (EAT). Pharmacological modulation of the GABAB receptor affected the levels of ATM infiltration and adipose tissue inflammation in IAT, but not in EAT, and GABA administration ameliorated systemic insulin resistance and enhanced insulin-dependent glucose uptake in IAT, accompanied by lower inflammatory responses. Intriguingly, compared with adipose-derived stem cells (ADSCs) from EAT, IAT-ADSCs played key roles in mediating GABA responses that repressed ATM infiltration in high-fat diet-fed mice. These data suggest that selective GABA responses in IAT contribute to fat depot-selective suppression of inflammatory responses and protection from insulin resistance in obesity.

scholarly journals In situ transplantation of adipose-derived stem cells via photoactivation improves glucose metabolism in obese mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luochen Zhu ◽  
Ziqian Feng ◽  
Xin Shu ◽  
Qian Gao ◽  
Jiaqi Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Epididymal Adipose Tissue ◽  
Adipose Derived Stem Cells ◽  
Combined Application

Abstract Background Accumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. However, therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. Methods We demonstrate that the effect of a combined application of photoactivation and adipose-derived stem cells (ASCs) using transplantation into visceral epididymal adipose tissue (EAT) in obesity. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Results In diet-induced obesity, implantation of light-treated ASCs improved glucose tolerance and ameliorated systemic insulin resistance. Intriguingly, compared with non-light-treated ASCs, light-treated ASCs reduced monocyte infiltration and the levels of ATMs in EAT. Moreover, implantation of light-treated ASCs exerts more anti-inflammatory effects by suppressing M1 polarization and enhancing macrophage M2 polarization in EAT. Mass spectrometry revealed that light-treated human obese ASCs conditioned medium retained a more complete secretome with significant downregulation of pro-inflammatory cytokines and chemokines. Conclusions These data suggest that the combined application of photoactivation and ASCs using transplantation into dysfunctional adipose tissue contribute to selective suppression of inflammatory responses and protection from insulin resistance in obesity and type 2 diabetes.

scholarly journals Are Adipose-Derived Stem Cells from Liver Falciform Ligaments Another Possible Source of Mesenchymal Stem Cells?

2017 ◽  
Vol 26 (5) ◽  
pp. 855-866 ◽  
Author(s):  
Sang Woo Lee ◽  
Jae Uk Chong ◽  
Seon Ok Min ◽  
Seon Young Bak ◽  
Kyung Sik Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Liver Disease ◽  
Subcutaneous Adipose Tissue ◽  
Falciform Ligament ◽  
Pcr Analysis ◽  
Marker Genes ◽  
Adipose Derived Stem Cells ◽  
Subcutaneous Adipose

Falciform ligaments in the liver are surrounded by adipose tissue. We investigated the capability of adipose-derived stem cells from human liver falciform ligaments (hLF-ADSCs) to differentiate into hepatic-type cells and confirmed the functional capacity of the cells. Mesenchymal stem cells (MSCs) were isolated from the liver falciform ligament and abdominal subcutaneous adipose tissue in patients undergoing partial hepatectomy for liver disease. Cells were cultivated in MSC culture medium. Properties of MSCs were confirmed by flow cytometry, RT-PCR analysis, immunocytochemistry assays, and multilineage differentiation. Hepatic induction was performed using a three-step differentiation protocol with various growth factors. Morphology, capacity for expansion, and characteristics were similar between hLF-ADSCs and adipose-derived stem cells from human abdominal subcutaneous adipose tissue (hAS-ADSCs). However, hematopoietic– and mesenchymal–epithelial transition (MET)-related surface markers (CD133, CD34, CD45, and E-cadherin) had a higher expression in hLF-ADSCs. The hepatic induction marker genes had a higher expression in hLF-ADSCs on days 7 and 10 after the hepatic induction. Albumin secretion was similar between hLF-ADSCs and hAS-ADSCs at 20 days after the hepatic induction. The hLF-ADSCs had a different pattern of surface marker expression relative to hAS-ADSCs. However, proliferation, multilineage capacity, and hepatic induction were similar between the cell types. Accordingly, it may be a useful source of MSCs for patients with liver disease.

Abstract 402: Human CD271-positive Adipose Derived Stem Cells are the Angiogenic Subset Decreased by Donor Insulin Resistance

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Oto Inoue ◽  
Soichiro Usui ◽  
Kosei Yamaguchi ◽  
Yusuke Takeda ◽  
Chiaki Goten ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Capillary Density ◽  
Adipose Derived Stem Cells ◽  
Knock Out ◽  
Healthy Donors ◽  
Knock Out Mice

Introduction: Type 2 diabetes mellitus (T2DM) is an important risk factor for cardiovascular diseases (CVDs). Recently, cell therapy using adipose-derived stem cells (ADSCs) has emerged as an attractive therapy for severe CVDs because of their angiogenic potentials. However, whether and how T2DM would impair human ADSC angiogenic capacity is still uncertain. We previously reported that CD31 - CD34 + CD271 + ADSCs (CD271 + ADSCs) were specifically decreased in adipose tissue of T2DM patients. Therefore, we aimed to investigate the angiogenic capacity of CD271 + ADSCs. Furthermore, we evaluate which patients’ parameters regard as T2DM would decrease the amount of CD271 + ADSCs. Methods and Results: Human CD45 - CD34 + CD31 - ADSCs were obtained from subcutaneous adipose tissue of healthy donors, separated into CD271 + and CD271 - subsets by FACS, and cultured. Both subsets of ADSCs were assessed gene expression profile by microarray. Microarray analysis and validation PCR elucidated that PI3K/Akt/mTOR pathway was significantly up-regulated in CD271 + ADSCs compared to in CD271 - ADSCs. ( p < 0.05). Then, we compared in vivo angiogenic capacity in xenograft experiments of nude mice subjected to hindlimb ischemia. Angiogenesis was evaluated histologically using perfused lectin (capillary density) at day 14. Cell therapy using CD271 + ADSCs demonstrated about 3-fold more lectin + capillaries compared to CD271 - ADSCs or PBS injection ( p < 0.005, n = 5 / group). Next, we established cultured ADSCs obtained from CD271 knock-out mice (KO-ADSCs) and compared their angiogenic capacity with those from WT mice. Consistently, KO-ADSCs demonstrated impaired in vivo angiogenic capacity ( p < 0.005, n = 5 / group). Finally, we collected 23 samples of adipose tissue obtained from CVD patients and evaluated the frequency of CD271 + ADSCs in CD45 - CD34 + CD31 - ADSCs. Among studied parameters, HOMA-IR, an index of insulin resistance, was negatively correlated with the frequency of CD271+ ADSCs ( r = -0.64, p < 0.005). Conclusions: Human CD271 + ADSCs demonstrated enhanced in vivo angiogenic capacity with higher mTOR expression. Donor insulin resistance might decrease this regenerative subset of ADSCs. These findings would be critical for development and improvement of ADSC therapy.

scholarly journals Role of Subcutaneous Adipose Tissue in the Pathogenesis of Insulin Resistance

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Pavankumar Patel ◽  
Nicola Abate
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
The United States ◽  
Relative Role ◽  
Functional Characteristics ◽  
Metabolic Complications ◽  
Fat Depot ◽  
Subcutaneous Adipose

Burden of obesity has increased significantly in the United States over last few decades. Association of obesity with insulin resistance and related cardiometabolic problems is well established. Traditionally, adipose tissue in visceral fat depot has been considered a major culprit in development of insulin resistance. However, growing body of the literature has suggested that adipose tissue in subcutaneous fat depot, not only due to larger volume but also due to inherent functional characteristics, can have significant impact on development of insulin resistance. There are significant differences in functional characteristics of subcutaneous abdominal/truncal versus gluteofemoral depots. Decreased capacity for adipocyte differentiation and angiogenesis along with adipocyte hypertrophy can trigger vicious cycle of inflammation in subcutaneous adipose tissue and subsequent ectopic fat deposition. It is important to shift focus from fat content to functional heterogeneity in adipose tissue depots to better understand the relative role of subcutaneous adipose tissue in metabolic complications of obesity. Therapeutic lifestyle change continues to be the most important intervention in clinical practice at any level of increased adiposity. Future pharmaceutical interventions aimed at improving adipose tissue function in various subcutaneous depots have potential to help maintain adequate insulin sensitivity and reduce risk for development of insulin resistance complications.

scholarly journals Subcutaneous Adipose Stem Cells in Obesity: The Impact of Bariatric Surgery

2021 ◽  
Author(s):  
Veronica Mocanu ◽  
Daniel V. Timofte ◽  
Ioana Hristov
Keyword(s):  
Insulin Resistance ◽  
Bariatric Surgery ◽  
Stem Cells ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Adipogenic Differentiation ◽  
Low Grade ◽  
Potential Weight ◽  
Subcutaneous Adipose ◽  
The Impact

Adipocyte expansion, which involves adipose tissue-derived mesenchymal stem cells (ASCs), is a critical process with implications in the pathogenesis of metabolic syndrome and insulin resistance associated with obesity. Impaired subcutaneous adipogenesis leads to dysfunctional, hypertrophic adipocytes, chronic low-grade inflammation, and peripheric insulin resistance. Alternatively, it has also been proposed that the preservation of the functionality of subcutaneous adipocyte precursors could contribute to some obese individuals remaining metabolically healthy. Very few studies evaluated the changes in the adipogenic differentiation for human subcutaneous ASCs following bariatric surgery. Weight loss after bariatric surgery involves extensive remodeling of adipose tissue, comprising the hyperplasia-hypertrophy balance. Subcutaneous ASCs may be implicated in the variations of bariatric outcomes, through a different restoration in their proliferative and adipogenic potential. Weight loss induced by bariatric surgery correlates to the subcutaneous ASC functions and could explain the variability of metabolic improvement. Limited research data are available to the present and these data support the importance of diagnosis of subcutaneous ASCs functions as predictors of metabolic improvement after bariatric surgery.

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).

scholarly journals Disruption of GIP/GIPR Axis in Human Adipose Tissue Is Linked to Obesity and Insulin Resistance

2014 ◽  
Vol 99 (5) ◽  
pp. E908-E919 ◽  
Author(s):  
Victòria Ceperuelo-Mallafré ◽  
Xavier Duran ◽  
Gisela Pachón ◽  
Kelly Roche ◽  
Lourdes Garrido-Sánchez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Human Adipose Tissue ◽  
Fat Cells ◽  
Model Assessment ◽  
Adipose Derived Stem Cells ◽  
Obese Patients ◽  
Insulin Sensitizer

Context: Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. Objective: Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. Design: GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. Results: GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. Conclusions: GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.

scholarly journals Characterization of adipose tissue macrophages and adipose-derived stem cells in critical wounds

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2824 ◽  
Author(s):  
Bong-Sung Kim ◽  
Pathricia V. Tilstam ◽  
Katrin Springenberg-Jung ◽  
Arne Hendrick Boecker ◽  
Corinna Schmitz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Adipose Tissue ◽  
Stem Cell ◽  
Subcutaneous Adipose Tissue ◽  
Stem Cell Markers ◽  
Adipose Derived Stem Cells ◽  
Cell Markers ◽  
Adipose Tissue Macrophages ◽  
Subcutaneous Adipose

Background Subcutaneous adipose tissue is a rich source of adipose tissue macrophages and adipose-derived stem cells which both play a key role in wound repair. While macrophages can be divided into the classically-activated M1 and the alternatively-activated M2 phenotype, ASCs are characterized by the expression of specific stem cell markers. Methods In the present study, we have investigated the expression of common macrophage polarization and stem cell markers in acutely inflamed adipose tissue. Subcutaneous adipose tissue adjacent to acutely inflamed wounds of 20 patients and 20 healthy subjects were harvested and underwent qPCR and flow cytometry analysis. Results Expression levels of the M1-specific markers CD80, iNOS, and IL-1b were significantly elevated in inflammatory adipose tissue when compared to healthy adipose tissue, whereas the M2-specific markers CD163 and TGF-β were decreased. By flow cytometry, a significant shift of adipose tissue macrophage populations towards the M1 phenotype was confirmed. Furthermore, a decrease in the mesenchymal stem cell markers CD29, CD34, and CD105 was observed whereas CD73 and CD90 remained unchanged. Discussion This is the first report describing the predominance of M1 adipose tissue macrophages and the reduction of stem cell marker expression in acutely inflamed, non-healing wounds.

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