Crosstalk between adipose tissue and blood vessels in cardiometabolic syndrome: implication of steroid hormone receptors (MR/GR)

AbstractCrosstalk between adipose tissue and blood vessels is vital to vascular homeostasis and is disturbed in cardiovascular and metabolic diseases such as hypertension, diabetes and obesity. Cardiometabolic syndrome (CMS) refers to the clustering of obesity-related metabolic disorders such as insulin resistance, glucose and lipid profile alterations, hypertension and cardiovascular diseases. Mechanisms underlying these associations remain unclear. Adipose tissue associated with the vasculature [known as perivascular adipose tissue (PVAT)] has been shown to produce myriads of adipose tissue-derived substances called adipokines, including hormones, cytokines and reactive oxygen species (ROS), which actively participate in the regulation of vascular function and local inflammation by endocrine and/or paracrine mechanisms. As a result, the signaling from PVAT to the vasculature is emerging as a potential therapeutic target for obesity and diabetes-related vascular dysfunction. Accumulating evidence supports a shift in our understanding of the crucial role of elevated plasma levels of aldosterone in obesity, promoting insulin resistance and hypertension. In obesity, aldosterone/mineralocorticoid receptor (MR) signaling induces an abnormal secretion of adipokines, ROS production and systemic inflammation, which in turn contribute to impaired insulin signaling, reduced endothelial-mediated vasorelaxation, and associated cardiovascular abnormalities. Thus, aldosterone excess exerts detrimental metabolic and vascular effects that participate to the development of the CMS and its associated cardiovascular abnormalities. In this review, we focus on the physiopathological roles of corticosteroid receptors in the interplay between PVAT and the vasculature, which underlies their potential as key regulators of vascular function.

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Perivascular Adipose Tissue and Cardiometabolic Disease

The Indonesian Biomedical Journal ◽

10.18585/inabj.v5i1.46 ◽

2013 ◽

Vol 5 (1) ◽

pp. 13

Author(s):

Anna Meiliana ◽

Andi Wijaya

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Blood Vessels ◽

Vascular Function ◽

Immune Cell ◽

The Body ◽

Cardiometabolic Disease ◽

Perivascular Adipose Tissue ◽

Nitric Oxide Signaling ◽

Fat Depots

BACKGROUND: Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity.CONTENT: Perivascular adipose tissue (PVAT) is a local deposit of adipose tissue surrounding the vasculature. PVAT is present throughout the body and has been shown to have a local effect on blood vessels. The influence of PVAT on the vasculature changes with increasing adiposity. PVAT similarly to other fat depots, is metabolically active, secreting a wide array of bioactive substances, termed ‘adipokines’. Adipokines include cytokines, chemokines and hormones that can act in a paracrine, autocrine or endocrine fashion. Many of the proinflammatory adipokines upregulated in obesity are known to influence vascular function, including endothelial function, oxidative stress, vascular stiffness and smooth muscle migration. Adipokines also stimulate immune cell migration into the vascular wall, potentially contributing to the inflammation found in atherosclerosis. Finally, adipokines modulate the effect of insulin on the vasculature, thereby decreasing insulin-mediated muscle glucose uptake. This leads to alterations in nitric oxide signaling, insulin resistance and potentially atherogenesis.SUMMARY: PVAT surrounds blood vessels. PVAT and the adventitial layer of blood vessels are in direct contact with each other. Healthy PVAT secretes adipokines and regulates vascular function. Obesity is associated with changes in adipokine secretion and the resultant inflammation of PVAT. The dysregulation of adipokines changes the effect of PVAT on the vasculature. Changes in perivascular adipokines secretion in obesity appear to contribute to the development of obesity-mediated vascular disease.KEYWORDS: obesity, perivascular adipose tissue, PVAT, cardiometabolic disease, adipokine

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Perivascular adipose tissue, inflammation and insulin resistance: link to vascular dysfunction and cardiovascular disease

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2015-0010 ◽

2015 ◽

Vol 22 (1) ◽

Cited By ~ 15

Author(s):

Guido Lastra ◽

Camila Manrique

Keyword(s):

Insulin Resistance ◽

Cardiovascular Disease ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Vascular Function ◽

Vascular Dysfunction ◽

Small Diameter ◽

Perivascular Adipose Tissue ◽

Anti Inflammatory ◽

Visceral Adipose

AbstractObesity is a leading risk factor for the development of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD), however the underlying mechanisms still remain to be fully uncovered. It is now well accepted that dysfunctional adipose tissue in conditions of obesity is a critical source of inflammation that impacts the cardiovascular system and contributes to CVD. Although traditionally visceral adipose tissue has been linked to increased CVD risk, there is mounting interest in the role that fat accumulation around the vasculature plays in the pathogenesis of vascular dysfunction. Perivascular adipose tissue (PVAT) is in intimate contact with large, medium and small diameter arterial beds in several tissues, and has been shown to control vascular function as well as remodeling. PVAT does not merely mirror visceral adipose tissue changes seen in obesity, but has unique features that impact vascular biology. In lean individuals PVAT exerts vasodilatory and anti-inflammatory functions, however obesity results in PVAT inflammation, characterized by imbalance between pro- and anti-inflammatory cells as wells as adipokines. PVAT inflammation promotes insulin resistance in the vasculature, thus resulting in impaired insulin-mediated vasodilatory responses and vascular remodeling. In this review we address current knowledge about the mechanisms that link PVAT inflammation to insulin resistance and vascular dysfunction. Indeed, PVAT emerges as a novel type of adipose tissue that participates in the pathogenesis of CVD, independently to a large extent to visceral adipose tissue.

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The steroid hormone receptors in tumors of adipose tissue

Journal of Surgical Oncology ◽

10.1002/jso.2930280203 ◽

1985 ◽

Vol 28 (2) ◽

pp. 87-89 ◽

Cited By ~ 5

Author(s):

P. K. Chaudhuri ◽

M. J. Walker ◽

C. W. Beattie ◽

T. K. Das Gupta

Keyword(s):

Adipose Tissue ◽

Hormone Receptors ◽

Steroid Hormone ◽

Steroid Hormone Receptors

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Perivascular adipose tissue modulates vascular function in the human internal thoracic artery

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2005.05.028 ◽

2005 ◽

Vol 130 (4) ◽

pp. 1130-1136 ◽

Cited By ~ 113

Author(s):

Yu-Jing Gao ◽

Zhao-hua Zeng ◽

Kevin Teoh ◽

Arya M. Sharma ◽

Labib Abouzahr ◽

...

Keyword(s):

Adipose Tissue ◽

Vascular Function ◽

Internal Thoracic Artery ◽

Perivascular Adipose Tissue

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Maternal separation enhances anticontractile perivascular adipose tissue function in male rats on a high-fat diet

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00197.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. R1085-R1095 ◽

Cited By ~ 1

Author(s):

Analia S. Loria ◽

Frank T. Spradley ◽

Ijeoma E. Obi ◽

Bryan K. Becker ◽

Carmen De Miguel ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Life Stress ◽

Vascular Function ◽

Maternal Separation ◽

Male Rats ◽

Protective Effects ◽

Ang Ii ◽

High Fat ◽

Perivascular Adipose Tissue

Clinical studies have shown that obesity negatively impacts large arteries’ function. We reported that rats exposed to maternal separation (MatSep), a model of early life stress, display enhanced angiotensin II (ANG II)-induced vasoconstriction in aortic rings cleaned of perivascular adipose tissue (PVAT) under normal diet (ND) conditions. We hypothesized that exposure to MatSep promotes a greater loss of PVAT-mediated protective effects on vascular function and loss of blood pressure (BP) rhythm in rats fed a high-fat diet (HFD) when compared with controls. MatSep was performed in male Wistar-Kyoto rats from days 2 to 14 of life. Normally reared littermates served as controls. On ND, aortic rings from MatSep rats with PVAT removed showed increased ANG II-mediated vasoconstriction versus controls; however, rings from MatSep rats with intact PVAT displayed blunted constriction. This effect was exacerbated by an HFD in both groups; however, the anticontractile effect of PVAT was greater in MatSep rats. Acetylcholine-induced relaxation was similar in MatSep and control rats fed an ND, regardless of the presence of PVAT. HFD impaired aortic relaxation in rings without PVAT from MatSep rats, whereas the presence of PVAT improved relaxation in both groups. On an HFD, immunolocalization of vascular smooth muscle-derived ANG-(1–7) and PVAT-derived adiponectin abundances were increased in MatSep. In rats fed an HFD, 24-h BP and BP rhythms were similar between groups. In summary, MatSep enhanced the ability of PVAT to blunt the heightened ANG II-induced vasoconstriction and endothelial dysfunction in rats fed an HFD. This protective effect may be mediated via the upregulation of vasoprotective factors within the adipovascular axis.

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Perivascular adipose tissue in vascular function

Journal of Cardiovascular Pharmacology ◽

10.1097/fjc.0000000000001027 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Edwyn O. Cruz-López ◽

Estrellita Uijl ◽

A.H. Jan Danser

Keyword(s):

Adipose Tissue ◽

Vascular Function ◽

Perivascular Adipose Tissue

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The role of uncoupling protein 2 in macrophages and its impact on obesity-induced adipose tissue inflammation and insulin resistance

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014868 ◽

2020 ◽

Vol 295 (51) ◽

pp. 17535-17548

Author(s):

Xanthe A. M. H. van Dierendonck ◽

Tiphaine Sancerni ◽

Marie-Clotilde Alves-Guerra ◽

Rinke Stienstra

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Macrophage Activation ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Obesity And Diabetes ◽

Adipose Tissue Macrophages

The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance.

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CTRP7 deletion attenuates obesity-linked glucose intolerance, adipose tissue inflammation, and hepatic stress

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00344.2016 ◽

2017 ◽

Vol 312 (4) ◽

pp. E309-E325 ◽

Cited By ~ 18

Author(s):

Pia S. Petersen ◽

Xia Lei ◽

Risa M. Wolf ◽

Susana Rodriguez ◽

Stefanie Y. Tan ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Glucose Metabolism ◽

Resistance Index ◽

Activity Level ◽

Low Grade ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Metabolic Role ◽

Obesity And Diabetes

Chronic low-grade inflammation and cellular stress are important contributors to obesity-linked metabolic dysfunction. Here, we uncover an immune-metabolic role for C1q/TNF-related protein 7 (CTRP7), a secretory protein of the C1q family with previously unknown function. In obese humans, circulating CTRP7 levels were markedly elevated and positively correlated with body mass index, glucose, insulin, insulin resistance index, hemoglobin A1c, and triglyceride levels. Expression of CTRP7 in liver was also significantly upregulated in obese humans and positively correlated with gluconeogenic genes. In mice, Ctrp7 expression was differentially modulated in various tissues by fasting and refeeding and by diet-induced obesity. A genetic loss-of-function mouse model was used to determine the requirement of CTRP7 for metabolic homeostasis. When fed a control low-fat diet, male or female mice lacking CTRP7 were indistinguishable from wild-type littermates. In obese male mice consuming a high-fat diet, however, CTRP7 deficiency attenuated insulin resistance and enhanced glucose tolerance, effects that were independent of body weight, metabolic rate, and physical activity level. Improved glucose metabolism in CTRP7-deficient mice was associated with reduced adipose tissue inflammation, as well as decreased liver fibrosis and cellular oxidative and endoplasmic reticulum stress. These results provide a link between elevated CTRP7 levels and impaired glucose metabolism, frequently associated with obesity. Inhibiting CTRP7 action may confer beneficial metabolic outcomes in the setting of obesity and diabetes.

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