The role of immune cells in the development of adipose tissue dysfunction in cardiovascular diseases

Adipose tissue dysfunction characterized by a loss of homeostatic functions It is observed in patients with obesity, insulin resistance and diabetes. In case of violation of the physiological properties in adipose tissue, an increased production of cytokines and chemokines occurs with the infiltration of tissue by immune cells. In turn, immune cells also produce cytokines, metalloproteinases, reactive oxygen species and chemokines, which are involved in tissue remodeling, cellular signal transduction and immunity regulation. The presence of inflammatory cells in adipose tissue affects organs and tissues. So in the blood vessels, inflammation of perivascular adipose tissue leads to vascular remodeling, superoxide production, endothelial dysfunction with loss of the bioavailability of nitric oxide, contributing to the development of various vascular diseases. In adipose tissue dysfunction, adipokines are also produced, such as leptin, resistin, and visfatin. These substances contribute to metabolic dysfunction, alter systemic homeostasis, sympathetic outflow, glucose regulation, and insulin sensitivity. Thus, the study of the mechanisms of interaction between immune cells and adipose tissue is promising and may be an important therapeutic target.

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Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty

Physiology ◽

10.1152/physiol.00012.2016 ◽

2017 ◽

Vol 32 (1) ◽

pp. 9-19 ◽

Cited By ~ 57

Author(s):

Michael B. Stout ◽

Jamie N. Justice ◽

Barbara J. Nicklas ◽

James L. Kirkland

Keyword(s):

Adipose Tissue ◽

Chronic Disease ◽

Immune Cell ◽

Sterile Inflammation ◽

Metabolic Dysfunction ◽

Adverse Health Outcomes ◽

Cytokines And Chemokines ◽

Inflammatory Status ◽

Adipose Tissue Dysfunction ◽

Age Related

Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP). These processes synergistically promote chronic sterile inflammation, insulin resistance, and lipid redistribution away from subcutaneous adipose tissue. Without intervention, these effects contribute to age-related systemic metabolic dysfunction, physical limitations, and frailty. Thus adipose tissue dysfunction may be a fundamental contributor to the elevated risk of chronic disease, disability, and adverse health outcomes with advancing age.

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44-OR: PAR2-Regulated MIF Secretion from Non-Immune Cells in Adipose Tissue Is a Key Mechanism Involved in the Development of Metabolic Dysfunction

Diabetes ◽

10.2337/db20-44-or ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 44-OR

Author(s):

YIHENG HUANG ◽

LIUJUN CHEN ◽

YADAN QI ◽

DAKE QI

Keyword(s):

Adipose Tissue ◽

Immune Cells ◽

Metabolic Dysfunction

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Inflammatory cells in perivascular adipose tissue and the integrity of the tunica media in atherosclerotic coronary arteries

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2019.4409 ◽

2019 ◽

Author(s):

Ruda Zorc-Pleskovič ◽

Marjeta Zorc ◽

Dušan Šuput ◽

Aleksandra Milutinović

Keyword(s):

Adipose Tissue ◽

Coronary Arteries ◽

Obstructive Coronary Artery Disease ◽

Inflammatory Cells ◽

Elastic Membrane ◽

Inflammatory Infiltration ◽

Perivascular Adipose Tissue ◽

Tunica Media ◽

External Elastic Membrane ◽

The Media

Obstructive coronary artery disease (CAD) is characterized by inflammation within the atherosclerotic coronary arteries. Infiltration of inflammatory cells into muscular media can lead to remodeling and weakening of the arterial wall. We examined the relationship between inflammatory infiltration in perivascular adipose tissue (PVAT), state of the external elastic membrane, and the intensity of inflammatory infiltration in the tunica media of coronary arteries obtained by endarterectomy from symptomatic patients with diffuse CAD. We analyzed endarterectomy sequesters from 22 coronary arteries that contained the intima, media, a part of the adventitia, and PVAT in at least one part of the sequester. The coronary arteries were divided into two groups according to the presence or absence of inflammatory infiltration in PVAT. Staining with hematoxylin-eosin and by the Movat's method showed atherosclerotic changes in the intima and media. Immunohistochemistry (anti-leukocyte common antigen [LCA] antibody) was used for the detection of leukocytes. We found a significant positive correlation between inflammatory infiltration in PVAT and preservation of the external elastic membrane of coronary arteries. Furthermore, we found a significant negative correlation between inflammatory infiltration in PVAT and the intensity of inflammatory infiltration in the media. It seems that the integrity of the external elastic membrane and the proinflammatory properties of PVAT restrain inflammatory cells within PVAT. Both effects may prevent the migration of inflammatory cells into the media and delay the development of CAD.

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B Lymphocytes and Adipose Tissue Inflammation

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.312467 ◽

2020 ◽

Vol 40 (5) ◽

pp. 1110-1122 ◽

Cited By ~ 1

Author(s):

Prasad Srikakulapu ◽

Coleen A. McNamara

Keyword(s):

Adipose Tissue ◽

B Cell ◽

Immune Cells ◽

Immune Cell ◽

Metabolic Dysfunction ◽

Adipose Tissue Inflammation ◽

Cell Type ◽

Tissue Inflammation ◽

B Cell Subsets

The immune system plays an important role in obesity-induced adipose tissue inflammation and the resultant metabolic dysfunction, which can lead to hypertension, dyslipidemia, and insulin resistance and their downstream sequelae of type 2 diabetes mellitus and cardiovascular disease. While macrophages are the most abundant immune cell type in adipose tissue, other immune cells are also present, such as B cells, which play important roles in regulating adipose tissue inflammation. This brief review will overview B-cell subsets, describe their localization in various adipose depots and summarize our knowledge about the function of these B-cell subsets in regulating adipose tissue inflammation, obesity-induced metabolic dysfunction and atherosclerosis.

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Irisin improves perivascular adipose tissue dysfunction via regulation of the heme oxygenase-1/adiponectin axis in diet-induced obese mice

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2016.09.005 ◽

2016 ◽

Vol 99 ◽

pp. 188-196 ◽

Cited By ~ 24

Author(s):

Ningning Hou ◽

Yihui Liu ◽

Fang Han ◽

Di Wang ◽

Xiaoshuang Hou ◽

...

Keyword(s):

Adipose Tissue ◽

Heme Oxygenase ◽

Heme Oxygenase 1 ◽

Obese Mice ◽

Perivascular Adipose Tissue ◽

Adipose Tissue Dysfunction

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Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines

ISRN Inflammation ◽

10.1155/2013/139239 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 385

Author(s):

Kassem Makki ◽

Philippe Froguel ◽

Isabelle Wolowczuk

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Immune Cells ◽

Metabolic Regulation ◽

Immune Cell ◽

Suppressor Cells ◽

Cell Types ◽

Immune Functions ◽

Cytokines And Chemokines ◽

Wide Range

Adipose tissue is a complex organ that comprises a wide range of cell types with diverse energy storage, metabolic regulation, and neuroendocrine and immune functions. Because it contains various immune cells, either adaptive (B and T lymphocytes; such as regulatory T cells) or innate (mostly macrophages and, more recently identified, myeloid-derived suppressor cells), the adipose tissue is now considered as a bona fide immune organ, at the cross-road between metabolism and immunity. Adipose tissue disorders, such as those encountered in obesity and lipodystrophy, cause alterations to adipose tissue distribution and function with broad effects on cytokine, chemokine, and hormone expression, on lipid storage, and on the composition of adipose-resident immune cell populations. The resulting changes appear to induce profound consequences for basal systemic inflammation and insulin sensitivity. The purpose of this review is to synthesize the current literature on adipose cell composition remodeling in obesity, which shows how adipose-resident immune cells regulate inflammation and insulin resistance—notably through cytokine and chemokine secretion—and highlights major research questions in the field.

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A TRAIL-TL1A paracrine network involving adipocytes, macrophages and lymphocytes induces adipose tissue dysfunction downstream of E2F1 in human obesity

10.2337/figshare.12709595 ◽

2020 ◽

Author(s):

Ada Admin ◽

Nitzan Maixner ◽

Tal Pecht ◽

Yulia Haim ◽

Vered Chalifa-Caspi ◽

...

Keyword(s):

Adipose Tissue ◽

Stromal Vascular Fraction ◽

Metabolic Dysfunction ◽

Trail Expression ◽

Adipose Tissue Dysfunction ◽

M1 Polarization ◽

Tnf Superfamily ◽

Diabetes Status ◽

Elevated Expression ◽

Visceral Adipose

Elevated expression of E2F1 in adipocyte-fraction of human visceral adipose-tissue(hVAT) associates with a poor cardio-metabolic profile. We hypothesized that beyond directly activating autophagy and MAP3K5(ASK)-MAP-kinase signaling, E2F1 governs a distinct transcriptome that contributes to adipose-tissue and metabolic dysfunction in obesity. We performed RNA-sequencing of hVAT samples from age-, sex- and BMI–matched patients, all obese, whose visceral-E2F1 protein expression was either high(E2F1high) or low(E2F1low). TNF-superfamily members, including TRAIL(TNFSF10), TL1A(TNFSF15) and their receptors were enriched in E2F1high. While TRAIL was equally expressed in adipocytes and stromal-vascular fraction(SVF), TL1A was mainly expressed in SVF, and TRAIL-induced TL1A was attributed to CD4+ and CD8+-subclasses of hVAT T-lymphocytes. In human adipocytes TL1A enhanced basal and impaired insulin-inhibitable lipolysis, and altered adipokine secretion, and in human macrophages induced foam-cells biogenesis and M1-polarization. Two independent human cohorts confirmed associations between TL1A and TRAIL expression in hVAT and higher leptin and IL6 serum concentrations, diabetes status, and hVAT-macrophage lipid content. Jointly, we propose an intra-adipose tissue E2F1-associated TNF-superfamily paracrine loop engaging lymphocytes, macrophages and adipocytes, ultimately contributing to adipose-tissue dysfunction in obesity.

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Potential role of perivascular adipose tissue in modulating atherosclerosis

Clinical Science ◽

10.1042/cs20190577 ◽

2020 ◽

Vol 134 (1) ◽

pp. 3-13 ◽

Cited By ~ 10

Author(s):

Samah Ahmadieh ◽

Ha Won Kim ◽

Neal L. Weintraub

Keyword(s):

Adipose Tissue ◽

Vascular Function ◽

Vessel Wall ◽

Potential Role ◽

Inflammatory Cells ◽

Protective Role ◽

Clinical Implications ◽

Blood Vessel Wall ◽

Perivascular Adipose Tissue

Abstract Perivascular adipose tissue (PVAT) directly juxtaposes the vascular adventitia and contains a distinct mixture of mature adipocytes, preadipocytes, stem cells, and inflammatory cells that communicate via adipocytokines and other signaling mediators with the nearby vessel wall to regulate vascular function. Cross-talk between perivascular adipocytes and the cells in the blood vessel wall is vital for normal vascular function and becomes perturbed in diseases such as atherosclerosis. Perivascular adipocytes surrounding coronary arteries may be primed to promote inflammation and angiogenesis, and PVAT phenotypic changes occurring in the setting of obesity, hyperlipidemia etc., are fundamentally important in determining a pathogenic versus protective role of PVAT in vascular disease. Recent discoveries have advanced our understanding of the role of perivascular adipocytes in modulating vascular function. However, their impact on cardiovascular disease (CVD), particularly in humans, is yet to be fully elucidated. This review will highlight the complex mechanisms whereby PVAT regulates atherosclerosis, with an emphasis on clinical implications of PVAT and emerging strategies for evaluation and treatment of CVD based on PVAT biology.

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