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

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.

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Adiposity and dyslipidaemia are associated with epigenetic age acceleration

Proceedings of The Nutrition Society ◽

10.1017/s0029665120003468 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Ana Arpón ◽

José-Ignacio Riezu-Boj ◽

Fermín I. Milagro ◽

José L. Santos ◽

J. Alfredo Martínez

Keyword(s):

Adipose Tissue ◽

Fat Mass ◽

Visceral Adipose Tissue ◽

Hdl Cholesterol ◽

Tissue Mass ◽

Age Related ◽

Epigenetic Age ◽

Adipose Tissue Mass ◽

Epigenetic Age Acceleration ◽

Visceral Adipose

AbstractAdipose tissue is an endocrine organ involved in a variety of regulatory functions beyond simple fat storage. Excessive fat accumulation in the visceral tissue has been related to obesity associated comorbidities and manifestations such as hypertension, hyperglycaemia, hypercholesterolemia, and inflammatory processes. In the later stages of life, there is a shift of fat distribution from subcutaneous to visceral depots, which is associated to the development of several age-related diseases. Epigenetics has been described as a potential contributor in aging processes, being also associated with diseases and fat deposition that progress with age. The aim of this research was to investigate the relationships between aging, epigenetic processes and visceral adipose tissue.The study population included 269 adult subjects recruited in the University of Navarra, Spain. Methylation data was assessed by Infinium MethylationEPIC beadchip from Illumina. Epigenetic age acceleration was calculated using the method GrimAge (AgeAccGrim), available in the website DNA methylation Age Calculator (https://dnamage.genetics.ucla.edu/home). Anthropometric, biochemical and blood pressure measurements were assessed following standardized methods. Body composition measurements by DXA were also carried out.Statistically significant correlations were found between age acceleration and waist circumference, some DXA-measured variables (lean mass, trunk fat mass, android fat mass, visceral adipose tissue mass), glucose, HDL-cholesterol, triglycerides levels and C-reactive protein. Linear regression models showed that visceral adipose tissue mass and HDL-cholesterol were conjointly influencing the epigenetic age acceleration. In addition, a mediation by HDL-cholesterol in the relationship between AgeAccGrim and visceral adipose tissue mass was found.Collectively, these findings demonstrated that visceral adiposity and dyslipidaemia are associated with accelerated aging effects, contributing to understand the development of age-related diseases.

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The Relationships of Plasma Adiponectin with a Favorable Lipid Profile, Decreased Inflammation, and Less Ectopic Fat Accumulation Depend on Adiposity

Clinical Chemistry ◽

10.1373/clinchem.2006.067397 ◽

2006 ◽

Vol 52 (10) ◽

pp. 1934-1942 ◽

Cited By ~ 54

Author(s):

Konstantinos Kantartzis ◽

Killian Rittig ◽

Bernd Balletshofer ◽

Jürgen Machann ◽

Fritz Schick ◽

...

Keyword(s):

Adipose Tissue ◽

Endothelial Function ◽

Visceral Adipose Tissue ◽

Hdl Cholesterol ◽

Ectopic Fat ◽

Fat Accumulation ◽

Plasma Adiponectin ◽

Markers Of Inflammation ◽

Visceral Adipose ◽

The Relationship

Abstract Background: The metabolic effects of adiponectin, including insulin sensitivity, seem to become stronger with increasing adiposity. Adiposity may also affect the relationship of adiponectin concentrations with serum lipid profile; markers of inflammation, atherosclerosis, and endothelial function; and ectopic fat accumulation. Methods: We measured plasma adiponectin concentrations, serum lipids, and serum markers of inflammation, atherosclerosis, and endothelial function in 242 Caucasians without type 2 diabetes. We also measured visceral adipose tissue with magnetic resonance tomography and liver and intramyocellular fat with 1H magnetic resonance spectroscopy. Results: We divided the study participants into 2 groups: lean [mean (SE) total body fat, 26% (0.6%); n = 119] and obese [36% (0.6%); n = 123]. In the obese group, plasma adiponectin concentrations showed a strong positive association with concentrations of HDL cholesterol (P <0.0001) and negative associations with LDL cholesterol, triglycerides, high-sensitivity C-reactive protein, interleukin 6, apolipoprotein B100, soluble E-selectin, soluble vascular cellular adhesion molecule 1, plasminogen activator inhibitor 1, leukocyte count, and liver and intramyocellular fat (all P <0.03). In the lean group, adiponectin showed a less strong association with HDL cholesterol (P = 0.005) and liver fat (P = 0.03) and no significant associations with the other variables (all P >0.10). High visceral adipose tissue was a strong predictor of low adiponectin concentrations, particularly in the obese group, and attenuated many of the significant relationships. Conclusions: High adiponectin plasma concentrations are associated with favorable lipid profiles, decreased subclinical inflammation, decreased markers of atherosclerosis and endothelial function, and low ectopic fat accumulation, particularly in obese persons. Adiponectin may also have a concentration-related effect on the relationship between visceral adipose tissue and these metabolic characteristics, especially in obese persons.

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Enlarged adipocytes from subcutaneous vs. visceral adipose tissue differentially contribute to metabolic dysfunction and atherogenic risk of patients with obesity

Scientific Reports ◽

10.1038/s41598-021-81289-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Juan Antonio Suárez-Cuenca ◽

Gustavo De La Peña-Sosa ◽

Karen De La Vega-Moreno ◽

Diana Zaineff Banderas-Lares ◽

Moisés Salamanca-García ◽

...

Keyword(s):

Diabetes Mellitus ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Multivariable Analysis ◽

Morphological Characteristics ◽

Hdl Cholesterol ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Adipocyte Size ◽

Visceral Adipose

AbstractMorphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT’s adipocytes showed a lower range of size expandability than VAT’s adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT’s larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT’s larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT’s larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.

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Tart Cherry Juice and Seeds Affect Pro-Inflammatory Markers in Visceral Adipose Tissue of High-Fat Diet Obese Rats

Molecules ◽

10.3390/molecules26051403 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1403

Author(s):

Michele Moruzzi ◽

Nora Klöting ◽

Matthias Blüher ◽

Ilenia Martinelli ◽

Seyed Khosrow Tayebati ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Inflammatory Markers ◽

Tart Cherry ◽

Positive Effects ◽

Inflammatory Status ◽

Study Results ◽

Major Player ◽

Visceral Adipose ◽

Tart Cherries

Background: Tart cherries (Prunus cerasus L.) are a rich source of anthocyanins. They are phytochemical flavonoids found in red and blue fruits, and vegetables that can reduce hyperlipidemia. Visceral Adipose Tissue (VAT) has emerged as a major player in driving obesity-related inflammatory response. Methods: This study has investigated the potential positive effects of tart cherries on rats with Diet-Induced Obesity (DIO). In particular, the inflammatory status in retroperitoneal (RPW) and perigonadal (PGW) adipose tissue were studied. Rats were fed ad libitum for 17 weeks with a hypercaloric diet with the supplementation of tart cherries seeds powder (DS) and seeds powder plus tart cherries juice containing 1mg of anthocyanins (DJS). In RPW and PGW, expression of CRP, IL-1 β, TNF-α, CCL2 and CD36, were measured by qRT-PCR, Western blot and immunohistochemistry techniques. Results: No differences in the weight of RPW and PGW animals were found between DS and DJS groups compared to DIO rats. However, an increase of inflammatory markers was observed in DIO group in comparison with control lean rats. A modulation of these markers was evident upon tart cherry supplementation. Conclusion: Study results suggest that tart cherry enriched-diet did not modify the accumulation of visceral fat, but it decreased inflammatory markers in both tissues. Therefore, this supplementation could be useful, in combination with healthy lifestyles, to modify adipose tissue cell metabolism limiting-obesity related organ damage.

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Inflammation in Atherosclerosis: From Theory to Practice

Bulletin of Science and Practice ◽

10.33619/2414-2948/59/21 ◽

2020 ◽

Vol 6 (10) ◽

pp. 186-205

Author(s):

A. Chaulin ◽

Ju. Grigoryeva

Keyword(s):

Risk Factors ◽

Adipose Tissue ◽

T Lymphocytes ◽

Inflammatory Cytokines ◽

Interferon Gamma ◽

Visceral Adipose Tissue ◽

Experimental Studies ◽

Therapeutic Interventions ◽

Inflammatory Status ◽

Visceral Adipose

Inflammation causes the formation, progression, and rupture of atherosclerotic plaques, which are an integral part of cardiovascular diseases. Numerous components are involved in the pathogenesis of atherosclerotic inflammation. Experimental studies have shown that the inflammatory subpopulation of monocytes / macrophages mainly accumulates in the atherosclerotic plaque and produces Pro-inflammatory cytokines that enhance atherogenesis. T-lymphocytes can contribute to the inflammatory processes that contribute to thrombosis by stimulating the production of collagen-destroying proteinases and a powerful procoagulant substance, tissue factor. Many research data link obesity, inflammation, and risk factors for atherosclerosis, which is a growing clinical concern given the increasing prevalence of obesity worldwide. Modulators of inflammation originating from visceral adipose tissue cause the liver to produce acute phase reagents involved in thrombosis. Additionally, levels of C-reactive protein increase with increasing levels of visceral adipose tissue. The adipose tissue of obese mice contains an increased number of macrophages and T-lymphocytes, increased activation of T-lymphocytes, and increased expression of interferon-gamma. It was found that interferon-gamma deficiency in mice reduces the production of inflammatory cytokines and the accumulation of inflammatory cells in adipose tissue. Another series of experiments on mice in vitro and in vivo confirmed that adiponectin, an adipocytokine whose plasma levels drop with obesity, acts as an endogenous anti-inflammatory modulator of both innate and acquired immunity in atherogenesis. Thus, the accumulation of experimental data confirms the key role of inflammation as a link between risk factors for atherosclerosis and the biology underlying the complications of this disease. A large Jupiter clinical trial confirms the clinical utility of assessing inflammatory status in therapeutic interventions to limit cardiovascular events. Thus, knowledge of the pathogenetic mechanisms underlying atherosclerotic inflammation is not only of theoretical value, but can also be used in practice when assessing the risk and prescribing therapy.

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Glucocorticoid-induced fingerprints on visceral adipose tissue transcriptome and epigenome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab662 ◽

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.

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