scholarly journals Adipose stem cells in obesity: challenges and opportunities

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Sunhye Shin ◽  
Asma S. El-Sabbagh ◽  
Brandon E. Lukas ◽  
Skylar J. Tanneberger ◽  
Yuwei Jiang
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Tissue Expansion ◽  
The Body ◽  
Adipose Stem Cells ◽  
Low Grade ◽  
Challenges And Opportunities ◽  
Adipose Tissue Remodeling

Abstract Adipose tissue, the storage of excessive energy in the body, secretes various proteins called adipokines, which connect the body’s nutritional status to the regulation of energy balance. Obesity triggers alterations of quantity and quality of various types of cells that reside in adipose tissue, including adipose stem cells (ASCs; referred to as adipose-derived stem/stromal cells in vitro). These alterations in the functionalities and properties of ASCs impair adipose tissue remodeling and adipose tissue function, which induces low-grade systemic inflammation, progressive insulin resistance, and other metabolic disorders. In contrast, the ability of ASCs to recruit new adipocytes when faced with caloric excess leads to healthy adipose tissue expansion, associated with lower amounts of inflammation, fibrosis, and insulin resistance. This review focuses on recent advances in our understanding of the identity of ASCs and their roles in adipose tissue development, homeostasis, expansion, and thermogenesis, and how these roles go awry in obesity. A better understanding of the biology of ASCs and their adipogenesis may lead to novel therapeutic targets for obesity and metabolic disease.

The Integrase Inhibitors Dolutegravir and Raltegravir Exert Proadipogenic and Profibrotic Effects and Induce Insulin Resistance in Human/Simian Adipose Tissue and Human Adipocytes

2020 ◽  
Vol 71 (10) ◽  
pp. e549-e560 ◽  
Author(s):  
Jennifer Gorwood ◽  
Christine Bourgeois ◽  
Valérie Pourcher ◽  
Guillaume Pourcher ◽  
Frédéric Charlotte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Adipose Stem Cells ◽  
Strand Transfer ◽  
Adipocyte Size ◽  
The Impact

Abstract Background Although some integrase strand transfer inhibitors (INSTIs) promote peripheral and central adipose tissue/weight gain in people with human immunodeficiency virus (PHIV), the underlying mechanism has not been identified. Here, we used human and simian models to assess the impact of INSTIs on adipose tissue phenotype and function. Methods Adipocyte size and fibrosis were determined in biopsies of subcutaneous and visceral adipose tissue (SCAT and VAT, respectively) from 14 noninfected macaques and 19 PHIV treated or not treated with an INSTI. Fibrosis, adipogenesis, oxidative stress, mitochondrial function, and insulin sensitivity were assessed in human proliferating or adipocyte-differentiated adipose stem cells after long-term exposure to dolutegravir or raltegravir. Results We observed elevated fibrosis, adipocyte size, and adipogenic marker expression in SCAT and VAT from INSTI-treated noninfected macaques. Adiponectin expression was low in SCAT. Accordingly, SCAT and VAT samples from INSTI-exposed patients displayed higher levels of fibrosis than those from nonexposed patients. In vitro, dolutegravir and, to a lesser extent, raltegravir were associated with greater extracellular matrix production and lipid accumulation in adipose stem cells and/or adipocytes as observed in vivo. Despite the INSTIs’ proadipogenic and prolipogenic effects, these drugs promoted oxidative stress, mitochondrial dysfunction, and insulin resistance. Conclusions Dolutegravir and raltegravir can directly impact adipocytes and adipose tissue. These INSTIs induced adipogenesis, lipogenesis, oxidative stress, fibrosis, and insulin resistance. The present study is the first to shed light on the fat modifications observed in INSTI-treated PHIV.

scholarly journals Chemotactic cytokines, obesity and type 2 diabetes:in vivoandin vitroevidence for a possible causal correlation?

2009 ◽  
Vol 68 (4) ◽  
pp. 378-384 ◽  
Author(s):  
Henrike Sell ◽  
Jürgen Eckel
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Low Grade ◽  
Obese Patients ◽  
Tissue Mass ◽  
Tissue Biology ◽  
Wide Range ◽  
Adipose Tissue Mass

A strong causal link between increased adipose tissue mass and insulin resistance in tissues such as liver and skeletal muscle exists in obesity-related disorders such as type 2 diabetes. Increased adipose tissue mass in obese patients and patients with diabetes is associated with altered secretion of adipokines, which also includes chemotactic proteins. Adipose tissue releases a wide range of chemotactic proteins including many chemokines and chemerin, which are interesting targets for adipose tissue biology and for biomedical research in obesity and obesity-related diseases. This class of adipokines may be directly linked to a chronic state of low-grade inflammation and macrophage infiltration in adipose tissue, a concept intensively studied in adipose tissue biology in recent years. The inflammatory state of adipose tissue in obese patients may be the most important factor linking increased adipose tissue mass to insulin resistance. Furthermore, chemoattractant adipokines may play an important role in this situation, as many of these proteins possess biological activity beyond the recruitment of immune cells including effects on adipogenesis and glucose homeostasis in insulin-sensitive tissues. The present review provides a summary of experimental evidence of the role of adipose tissue-derived chemotactic cytokines and their function in insulin resistancein vivoandin vitro.

Adipose Stem Cells from Lipedema and Control Adipose Tissue Respond Differently to Adipogenic Stimulation In Vitro

2019 ◽  
Vol 144 (3) ◽  
pp. 623-632 ◽  
Author(s):  
Anna-Theresa Bauer ◽  
Dominik von Lukowicz ◽  
Katrin Lossagk ◽  
Ursula Hopfner ◽  
Manuela Kirsch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Adipose Stem Cells ◽  
And Control

scholarly journals PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans

2020 ◽  
Vol 12 (571) ◽  
pp. eaay4145 ◽  
Author(s):  
Raziel Rojas-Rodriguez ◽  
Rachel Ziegler ◽  
Tiffany DeSouza ◽  
Sana Majid ◽  
Aylin S. Madore ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Gestational Diabetes ◽  
Signaling Pathway ◽  
Physiological State ◽  
Tissue Remodeling ◽  
Tissue Expansion ◽  
Dependent Manner ◽  
Adipose Tissue Remodeling

Pregnancy is a physiological state of continuous adaptation to changing maternal and fetal nutritional needs, including a reduction of maternal insulin sensitivity allowing for appropriately enhanced glucose availability to the fetus. However, excessive insulin resistance in conjunction with insufficient insulin secretion results in gestational diabetes mellitus (GDM), greatly increasing the risk for pregnancy complications and predisposing both mothers and offspring to future metabolic disease. Here, we report a signaling pathway connecting pregnancy-associated plasma protein A (PAPPA) with adipose tissue expansion in pregnancy. Adipose tissue plays a central role in the regulation of insulin sensitivity, and we show that, in both mice and humans, pregnancy caused remodeling of adipose tissue evidenced by altered adipocyte size, vascularization, and in vitro expansion capacity. PAPPA is known to be a metalloprotease secreted by human placenta that modulates insulin-like growth factor (IGF) bioavailability through prolteolysis of IGF binding proteins (IGFBPs) 2, 4, and 5. We demonstrate that recombinant PAPPA can stimulate ex vivo human adipose tissue expansion in an IGFBP-5– and IGF-1–dependent manner. Moreover, mice lacking PAPPA displayed impaired adipose tissue remodeling, pregnancy-induced insulin resistance, and hepatic steatosis, recapitulating multiple aspects of human GDM. In a cohort of 6361 pregnant women, concentrations of circulating PAPPA are inversely correlated with glycemia and odds of developing GDM. These data identify PAPPA and the IGF signaling pathway as necessary for the regulation of maternal adipose tissue physiology and systemic glucose homeostasis, with consequences for long-term metabolic risk and potential for therapeutic use.

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.

scholarly journals D-Mannose Inhibits Adipogenic Differentiation of Adipose Tissue-Derived Stem Cells via the miR669b/MAPK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yitong Liu ◽  
Lijia Guo ◽  
Lei Hu ◽  
Chen Xie ◽  
Jingfei Fu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Mapk Pathway ◽  
Adipogenic Differentiation ◽  
Tissue Expansion ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
Venn Diagram

The adipogenic differentiation of adipose tissue-derived stem cells (ADSCs) plays an important role in the process of obesity and host metabolism. D-Mannose shows a potential regulating function for fat tissue expansion and glucose metabolism. To explore the mechanisms through which D-mannose affects the adipogenic differentiation of adipose-derived stem cells in vitro, we cultured the ADSCs with adipogenic medium inducement containing D-mannose or glucose as the control. The adipogenic differentiation specific markers Pparg and Fabp4 were determined by real-time PCR. The Oil Red O staining was applied to measure the lipid accumulation. To further explore the mechanisms, microarray analysis was performed to detect the differences between glucose-treated ADSCs (G-ADSCs) and D-mannose-treated ADSCs (M-ADSCs) in the gene expression level. The microarray data were further analyzed by a Venn diagram and Gene Set Enrichment Analysis (GSEA). MicroRNA inhibitor transfection was used to confirm the role of key microRNA. Results. D-Mannose intervention significantly inhibited the adipogenic differentiation of ADSCs, compared with the glucose intervention. Microarray showed that D-mannose increased the expression of miR669b, which was an inhibitor of adipogenesis. In addition, GSEA and western blot suggested that D-mannose suppressed the adipogenic differentiation via inhibiting the MAPK pathway and further inhibited the expression of proteins related to glucose metabolism and tumorigenesis. Conclusion. D-Mannose inhibits adipogenic differentiation of ADSCs via the miR669b/MAPK signaling pathway and may be further involved in the regulation of glucose metabolism and the inhibition of tumorigenesis.

scholarly journals SIV Infection and the HIV Proteins Tat and Nef Induce Senescence in Adipose Tissue and Human Adipose Stem Cells, Resulting in Adipocyte Dysfunction

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 854 ◽  
Author(s):  
Jennifer Gorwood ◽  
Tina Ejlalmanesh ◽  
Christine Bourgeois ◽  
Matthieu Mantecon ◽  
Cindy Rose ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Viral Proteins ◽  
Adipose Stem Cells ◽  
Siv Infection ◽  
P53 Activation ◽  
Human Adipose Stem Cells ◽  
P16 Expression

Background: Aging is characterized by adipose tissue senescence, inflammation, and fibrosis, with trunk fat accumulation. Aging HIV-infected patients have a higher risk of trunk fat accumulation than uninfected individuals—suggesting that viral infection has a role in adipose tissue aging. We previously demonstrated that HIV/SIV infection and the Tat and Nef viral proteins were responsible for adipose tissue fibrosis and impaired adipogenesis. We hypothesized that SIV/HIV infection and viral proteins could induce adipose tissue senescence and thus lead to adipocyte dysfunctions. Methods: Features of tissue senescence were evaluated in subcutaneous and visceral adipose tissues of SIV-infected macaques and in human adipose stem cells (ASCs) exposed to Tat or Nef for up to 30 days. Results: p16 expression and p53 activation were higher in adipose tissue of SIV-infected macaques than in control macaques, indicating adipose tissue senescence. Tat and Nef induced higher senescence in ASCs, characterized by higher levels of senescence-associated beta-galactosidase activity, p16 expression, and p53 activation vs. control cells. Treatment with Tat and Nef also induced oxidative stress and mitochondrial dysfunction. Prevention of oxidative stress (using N-acetyl-cysteine) reduced senescence in ASCs. Adipocytes having differentiated from Nef-treated ASCs displayed alterations in adipogenesis with lower levels of triglyceride accumulation and adipocyte marker expression and secretion, and insulin resistance. Conclusion: HIV/SIV promotes adipose tissue senescence, which in turn may alter adipocyte function and contribute to insulin resistance.

scholarly journals Effects of des-acyl ghrelin on insulin sensitivity and macrophage polarization in adipose tissue

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Fang Yuan ◽  
Qianqian Zhang ◽  
Haiyan Dong ◽  
Xinxin Xiang ◽  
Weizhen Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
The Body ◽  
Control Group ◽  
Low Grade ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Arginase 1 ◽  
Acyl Ghrelin

Abstract Background and Objectives Obesity is the accumulation of adipose tissue caused by excess energy in the body, accompanied by long-term chronic low-grade inflammation of adipose tissue. More than 50% of interstitial cells in adipose tissue are macrophages, which produce cytokines closely related to insulin resistance. Macrophage biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2 (anti-inflammatory). This study aimed to investigate the effect of gastric hormone des-acyl ghrelin (DAG) on the polarization phenotype of macrophages and elucidate the role of macrophages in adipose tissue inflammation and insulin sensitivity and its molecular mechanism. Methods Mice were subcutaneously administrated with DAG in osmotic minipumps. The mice were fed a normal diet or a high-fat diet (HFD). Different macrophage markers were detected by real-time revere transcription polymerase chain reaction. Results Exogenous administration of DAG significantly inhibited the increase of adipocyte volume caused by HFD and reduced the number of rosette-like structures in adipose tissue. HFD in the control group significantly increased M1 macrophage markers, tumor necrosis factor α (TNFα), and inducible NO synthase (iNOS). However, these increases were reduced or even reversed after DAG administration in vitro. The M2 markers, macrophage galactose type C-type Lectin-1 (MGL1), arginase 1 (Arg1), and macrophage mannose receptor 1 (MRC1) were decreased by HFD, and the downward trend was inhibited or reversed after DAG administration. Although Arg1 was elevated after HFD, the fold increase after DAG administration in vitro was much greater than that in the control group. Conclusion DAG inhibits adipose tissue inflammation caused by HFD, reduces infiltration of macrophages in adipose tissue, and promotes polarization of macrophages to M2, thus alleviating obesity and improving insulin sensitivity.

Do adipose tissue macrophages promote insulin resistance or adipose tissue remodelling in humans?

2014 ◽  
Vol 20 (1) ◽  
Author(s):  
Leonie K. Heilbronn ◽  
Bo Liu
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Tissue Expansion ◽  
Macrophage Infiltration ◽  
Low Grade ◽  
Tissue Remodelling ◽  
Inflammatory Phenotype ◽  
Inflammatory State ◽  
Caloric Excess

AbstractIn diet induced and genetically obese rodent models, adipose tissue is associated with macrophage infiltration, which promotes a low grade inflammatory state and the development of insulin resistance. In humans, obesity is also closely linked with macrophage infiltration in adipose tissue, a pro-inflammatory phenotype and insulin resistance. However, whether macrophage infiltration is a direct contributor to the development of insulin resistance that occurs in response to weight gain, or is a later consequence of the obese state is unclear. There are a number of concomitant changes that occur during adipose tissue expansion, including the number and size of adipocytes, the vasculature and the extracellular matrix. In this review, we will examine evidence for and against the role of macrophage recruitment into adipose tissue in promoting the development of insulin resistance in rodents and humans, as well as discuss the emerging role of macrophages in mediating healthy adipose tissue expansion during periods of caloric excess.

scholarly journals Roles of the Chemokine System in Development of Obesity, Insulin Resistance, and Cardiovascular Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Longbiao Yao ◽  
Oana Herlea-Pana ◽  
Janet Heuser-Baker ◽  
Yitong Chen ◽  
Jana Barlic-Dicen
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Nutrient Intake ◽  
Nutrient Deficiency ◽  
Tissue Expansion ◽  
Low Grade ◽  
Chemokine Production ◽  
Increase Risk

The escalating epidemic of obesity has increased the incidence of obesity-induced complications to historically high levels. Adipose tissue is a dynamic energy depot, which stores energy and mobilizes it during nutrient deficiency. Excess nutrient intake resulting in adipose tissue expansion triggers lipid release and aberrant adipokine, cytokine and chemokine production, and signaling that ultimately lead to adipose tissue inflammation, a hallmark of obesity. This low-grade chronic inflammation is thought to link obesity to insulin resistance and the associated comorbidities of metabolic syndrome such as dyslipidemia and hypertension, which increase risk of type 2 diabetes and cardiovascular disease. In this review, we focus on and discuss members of the chemokine system for which there is clear evidence of participation in the development of obesity and obesity-induced pathologies.

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