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.

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 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.

scholarly journals Adipokines: mechanisms of metabolic and behavioral disorders

2018 ◽  
Vol 15 (3) ◽  
pp. 14-20
Author(s):  
Yassine Chahirou ◽  
Abdelhalim Mesfioui ◽  
Ali Ouichou ◽  
Aboubaker Hessni
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Behavioral Disorders ◽  
Health Problems ◽  
Endocrine Tissue ◽  
Physiological Functions ◽  
Relationship Of ◽  
The Relationship

Current studies show that metabolic and behavioral disorders represent severe health problems. Several questions arise about the molecular relationship of metabolic and behavioral disorders. This review will discuss the relationship of lipid metabolism and fructose consumption accompanied by an increase in weight as well as associated disorders: hypertension, insulin-resistance, oxidative stress and depression. Adipose tissue is considered as an endocrine tissue with intense secretory activities (metabolic and inflammatory). These adipokines are responsible for an alteration of several physiological functions. In this review we will try to understand how lipogenesis that causes dyslipidemia can influence insulin resistance, hypertension, oxidative stress, depression and the relationship between these various disorders.

scholarly journals Modulation of Human Adipose Stem Cells’ Neurotrophic Capacity Using a Variety of Growth Factors for Neural Tissue Engineering Applications: Axonal Growth, Transcriptional, and Phosphoproteomic Analyses In Vitro

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1939
Author(s):  
Katharina M. Prautsch ◽  
Alexander Schmidt ◽  
Viola Paradiso ◽  
Dirk J. Schaefer ◽  
Raphael Guzman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Neurotrophic Factor ◽  
Axonal Growth ◽  
Cellular Level ◽  
Adipose Stem Cells ◽  
Transcriptional Analysis ◽  
Axonal Outgrowth ◽  
Human Adipose Stem Cells

We report on a potential strategy involving the exogenous neurotrophic factors (NTF) for enhancing the neurotrophic capacity of human adipose stem cells (ASC) in vitro. For this, ASC were stimulated for three days using NTF, i.e., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), NT4, glial cell-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF). The resulting conditioned medium (CM) as well as individual NTF exhibited distinct effects on axonal outgrowth from dorsal root ganglion (DRG) explants. In particular, CM derived from NT3-stimulated ASC (CM-NT3-ASC) promoted robust axonal outgrowth. Subsequent transcriptional analysis of DRG cultures in response to CM-NT3-ASC displayed significant upregulation of STAT-3 and GAP-43. In addition, phosphoproteomic analysis of NT3-stimulated ASC revealed significant changes in the phosphorylation state of different proteins that are involved in cytokine release, growth factors signaling, stem cell maintenance, and differentiation. Furthermore, DRG cultures treated with CM-NT3-ASC exhibited significant changes in the phosphorylation levels of proteins involved in tubulin and actin cytoskeletal pathways, which are crucial for axonal growth and elongation. Thus, the results obtained at the transcriptional, proteomic, and cellular level reveal significant changes in the neurotrophic capacity of ASC following NT3 stimulation and provide new options for improving the axonal growth-promoting potential of ASC in vitro.

scholarly journals Strategies for the hypothermic preservation of cell sheets of human adipose stem cells

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0222597 ◽  
Author(s):  
Sara Freitas-Ribeiro ◽  
Andreia Filipa Carvalho ◽  
Marina Costa ◽  
Mariana Teixeira Cerqueira ◽  
Alexandra Pinto Marques ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Stem Cells ◽  
Cell Sheets ◽  
Hypothermic Preservation ◽  
Human Adipose Stem Cells
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