scholarly journals Glucocorticoid-induced fingerprints on visceral adipose tissue transcriptome and epigenome

2021 ◽  
Author(s):  
Guillermo García-Eguren ◽  
Mar González-Ramírez ◽  
Pedro Vizán ◽  
Oriol Giró ◽  
Arturo Vega-Beyhart ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Histone Modifications ◽  
Visceral Adipose Tissue ◽  
Transcriptional Activation ◽  
Clock Genes ◽  
Adverse Outcomes ◽  
Low Grade ◽  
Inflammatory Status ◽  
Visceral Adipose ◽  
Epigenetic Signatures

Abstract Context & Objective Chronic glucocorticoid (GC) overexposure, resulting from endogenous Cushing’s syndrome (CS) or exogenous GC therapy, causes several adverse outcomes, including persistent central fat accumulation associated with a low-grade inflammation. However, no previous multi-omics studies in visceral adipose tissue (VAT) from patients exposed to high levels of unsuppressed GC during active CS or after remission are available yet. Methods We employed a translational approach combining high-throughput data on endogenous CS patients and a reversible CS mouse model. We performed RNA-seq and ChIP-seq on histone modifications (H3K4me3, H3K27ac and H3K27me3) to identify persistent transcriptional and epigenetic signatures in VAT produced during active CS and maintained after remission. Results VAT dysfunction was associated with low-grade pro-inflammatory status, macrophage infiltration and extracellular matrix remodeling. Most notably, chronic hypercortisolism caused a persistent circadian rhythm disruption in VAT through core clock genes modulation. Importantly, changes in the levels of two histone modifications associated to gene transcriptional activation (H3K4me3 and H3K27ac) correlated with the observed differences in gene expression during active CS and after CS remission. Conclusion We identified for the first time, the persistent transcriptional and epigenetic signatures induced by hypercortisolism in VAT, providing a novel integrated view of molecular components driving the long-term VAT impairment associated with CS.

Non-HDL cholesterol relates to pro-inflammatory status of human visceral adipose tissue

2016 ◽  
Vol 252 ◽  
pp. e182
Author(s):  
R. Poledne ◽  
I. Kralova Lesna ◽  
A. Kralova ◽  
A. Sekerkova ◽  
J. Fronek
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Hdl Cholesterol ◽  
Inflammatory Status ◽  
Visceral Adipose

Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral Adipose Tissue of 5α-Dihydrotestosterone-Induced Animal Model of Polycystic Ovary Syndrome

2017 ◽  
Vol 125 (08) ◽  
pp. 522-529 ◽  
Author(s):  
Danijela Milutinović ◽  
Marina Nikolić ◽  
Nataša Veličković ◽  
Ana Djordjevic ◽  
Biljana Bursać ◽  
...  
Keyword(s):  
Animal Model ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Abdominal Obesity ◽  
Visceral Adipose Tissue ◽  
Polycystic Ovary ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Visceral Adipose

AbstractPolycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity.

scholarly journals COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Adèle Lasbleiz ◽  
Bénédicte Gaborit ◽  
Astrid Soghomonian ◽  
Axel Bartoli ◽  
Patricia Ancel ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Intensive Care ◽  
Inflammatory Cytokines ◽  
Visceral Adipose Tissue ◽  
Cardiovascular Events ◽  
Low Grade ◽  
Viral Spread ◽  
Visceral Adipose ◽  
Pro Inflammatory Cytokines

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the “cytokine storm” and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.

scholarly journals Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 892
Author(s):  
Zaida Abad-Jiménez ◽  
Sandra López-Domènech ◽  
Rubén Díaz-Rúa ◽  
Francesca Iannantuoni ◽  
Segundo Ángel Gómez-Abril ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Diabetic Patients ◽  
Low Grade ◽  
Obese Patients ◽  
Visceral Adipose

Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFα, IL6, IL1β and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)). A reduction in protein levels of MCP1, NFκB, NLRP3, ASC, ATG5, Beclin1 and CHOP and an increase in p62 were also observed in the VAT of the diabetic group. This downregulation of both the NLRP3 inflammasome and autophagy in VAT may be associated with the improved inflammatory profile and leukocyte homeostasis seen in obese T2D patients treated with metformin with respect to MHO subjects and endorses the cardiometabolic protective effect of this drug.

scholarly journals The Inflammasome and Caspase-1 Activation: A New Mechanism Underlying Increased Inflammatory Activity in Human Visceral Adipose Tissue

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3769-3778 ◽  
Author(s):  
Tim B. Koenen ◽  
Rinke Stienstra ◽  
Lambertus J. van Tits ◽  
Leo A. B. Joosten ◽  
Jeroen F. van Velzen ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Cd8 T Cells ◽  
Nucleotide Binding ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Inflammatory Status ◽  
Visceral Adipose ◽  
Oligomerization Domain

The immune competent abdominal adipose tissue, either stored viscerally [visceral adipose tissue (VAT)] or sc [sc adipose tissue (SAT)], has been identified as a source of IL-1β and IL-18. To become active, the proforms of these cytokines require processing by caspase-1, which itself is mediated by the inflammasome. In this descriptive study, we investigate the expression of inflammasome components and caspase-1 in human fat and determine whether caspase-1 activity contributes to the enhanced inflammatory status of VAT. Paired SAT and VAT biopsies from 10 overweight subjects (body mass index, 25–28 kg/m2) were used to study the cellular composition and the intrinsic inflammatory capacity of both adipose tissue depots. The percentage of CD8+ T cells within the lymphocyte fraction was significantly higher in VAT compared with SAT (41.6 vs. 30.4%; P < 0.05). Adipose tissue cultures showed a higher release of IL-1β (10-fold; P < 0.05), IL-18 (3-fold; P < 0.05), and IL-6 and IL-8 (3-fold, P < 0.05; and 4-fold, P < 0.05, respectively) from VAT compared with SAT that was significantly reduced by inhibiting caspase-1 activity. In addition, caspase-1 activity was 3-fold (P < 0.05) higher in VAT compared with SAT, together with an increase in the protein levels of the inflammasome members apoptosis-associated speck-like protein containing a C-terminal caspase-recruitment domain (2-fold; P < 0.05) and nucleotide-binding oligomerization domain- like receptor pyrin domain containing 3 (2-fold; nonsignificant). Finally, caspase-1 activity levels were positively correlated with the percentage of CD8+ T cells present in adipose tissue. Our results show that caspase-1 and nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 inflammasome members are abundantly present in human VAT. The increased intrinsic caspase-1 activity in VAT represents a novel and specific inflammatory pathway that may determine the proinflammatory character of this specific depot.

scholarly journals Evidence for activation of inflammatory lipoxygenase pathways in visceral adipose tissue of obese Zucker rats

2011 ◽  
Vol 300 (1) ◽  
pp. E175-E187 ◽  
Author(s):  
Swarup K. Chakrabarti ◽  
Yeshao Wen ◽  
Anca D. Dobrian ◽  
Banumathi K. Cole ◽  
Qian Ma ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Genetic Model ◽  
Leukotriene B4 ◽  
Zucker Rats ◽  
Low Grade ◽  
The Metabolic Syndrome ◽  
Obese Zucker Rats ◽  
Visceral Adipose

Central obesity is associated with low-grade inflammation that promotes type 2 diabetes and cardiovascular disease in obese individuals. The 12- and 5-lipoxygenase (12-LO and 5-LO) enzymes have been linked to inflammatory changes, leading to the development of atherosclerosis. 12-LO has also been linked recently to inflammation and insulin resistance in adipocytes. We analyzed the expression of LO and proinflammatory cytokines in adipose tissue and adipocytes in obese Zucker rats, a widely studied genetic model of obesity, insulin resistance, and the metabolic syndrome. mRNA expression of 12-LO, 5-LO, and 5-LO-activating protein (FLAP) was upregulated in adipocytes and adipose tissue from obese Zucker rats compared with those from lean rats. Concomitant with increased LO gene expression, the 12-LO product 12-HETE and the 5-LO products 5-HETE and leukotriene B4 (LTB4) were also increased in adipocytes. Furthermore, upregulation of key proinflammatory markers interleukin (IL)-6, TNFα, and monocyte chemoattractant protein-1 were observed in adipocytes isolated from obese Zucker rats. Immunohistochemistry indicated that the positive 12-LO staining in adipose tissue represents cells in addition to adipocytes. This was confirmed by Western blotting in stromal vascular fractions. These changes were in part reversed by the novel anti-inflammatory drug lisofylline (LSF). LSF also reduced p-STAT4 in visceral adipose tissue from obese Zucker rats and improved the metabolic profile, reducing fasting plasma glucose and increasing insulin sensitivity in obese Zucker rats. In 3T3-L1 adipocytes, LSF abrogated the inflammatory response induced by LO products. Thus, therapeutic agents reducing LO or STAT4 activation may provide novel tools to reduce obesity-induced inflammation.

scholarly journals Visceral Adipose Tissue and Different Measures of Adiposity in Different Severities of Diffuse Idiopathic Skeletal Hyperostosis

2021 ◽  
Vol 11 (7) ◽  
pp. 663
Author(s):  
Netanja Harlianto ◽  
Jan Westerink ◽  
Wouter Foppen ◽  
Marjolein Hol ◽  
Rianne Wittenberg ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Smoking Status ◽  
Diffuse Idiopathic Skeletal Hyperostosis ◽  
Subcutaneous Fat ◽  
Low Grade ◽  
Negatively Associated ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Background: Diffuse idiopathic skeletal hyperostosis (DISH) is associated with both obesity and type 2 diabetes. Our objective was to investigate the relation between DISH and visceral adipose tissue (VAT) in particular, as this would support a causal role of insulin resistance and low grade inflammation in the development of DISH. Methods: In 4334 patients with manifest vascular disease, the relation between different adiposity measures and the presence of DISH was compared using z-scores via standard deviation logistic regression analyses. Analyses were stratified by sex and adjusted for age, systolic blood pressure, diabetes, non-HDL cholesterol, smoking status, and renal function. Results: DISH was present in 391 (9%) subjects. The presence of DISH was associated with markers of adiposity and had a strong relation with VAT in males (OR: 1.35; 95%CI: 1.20–1.54) and females (OR: 1.43; 95%CI: 1.06–1.93). In males with the most severe DISH (extensive ossification of seven or more vertebral bodies) the association between DISH and VAT was stronger (OR: 1.61; 95%CI: 1.31–1.98), while increased subcutaneous fat was negatively associated with DISH (OR: 0.65; 95%CI: 0.49–0.95). In females, increased subcutaneous fat was associated with the presence of DISH (OR: 1.43; 95%CI: 1.14–1.80). Conclusion: Markers of adiposity, including VAT, are strongly associated with the presence of DISH. Subcutaneous adipose tissue thickness was negatively associated with more severe cases of DISH in males, while in females, increased subcutaneous adipose tissue was associated with the presence of DISH.

Sign in / Sign up

Export Citation Format

Share Document