Protective Role of Perivascular Adipose Tissue in Endothelial Dysfunction and Insulin-Induced Vasodilatation of Hypercholesterolemic LDL Receptor-Deficient Mice

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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Adipose extracellular signal-regulated kinase 2 protected from endothelial dysfunction and the oxidative stress of perivascular adipose tissue in obese mice

European Heart Journal ◽

10.1093/ehjci/ehaa946.3822 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Osaki ◽

Y Sato ◽

S Endo ◽

K Ito ◽

K Kagami ◽

...

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Endothelial Dysfunction ◽

Mrna Levels ◽

Obese Mice ◽

Fatty Acid Binding ◽

Perivascular Adipose Tissue ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal

Abstract Introduction Extracellular signal-regulated kinase (ERK) modulates differentiation and maturation of adipocyte and the hypertrophy and differentiation of adipocytes affected the vascular diseases in obese. Changes in characters of adipocytes could develope the oxidative stress and inflammations. Moreover, changes in perivascular adipose tissue (PVAT) could modulate vascular tonus in obesity. However, the role of adipose ERK2 in endothelial function and characters of PVAT in obese in vivo had not been clarified, yet. Purpose This study aims to elucidate the role of the adipose ERK2 in endothelial-dependent relaxation (EDR) in mice model of obesity. The role of PVAT in EDR was also assessed. Methods and results We created adipose-specific ERK2 knock out mice (AE2KO) by crossing fatty acid binding protein 4 Cre and ERK2 flox mice and fed them with normal diet (ND) or high fat/ high sucrose diet (HFHSD) for 24 weeks. AE2KO fed with HFHSD gained more weight and revealed the heterogeneity in sizes of adipocyte in subcutaneous fat (SF). Furthermore, the mRNA levels of lipoprotein lipase, hormone-sensitive lipase, and peroxisome proliferator-activated receptor γ, which was the master genes of adipocyte differentiation, were markedly down-regulated in SF. PVAT in AE2KO with HFHSD was markedly enlarged and the mRNA expression of inflammatory adipocytokines, such as IL-1β and leptin were up-regulated. Next, we assessed EDR by acetylcholine (ACh) -induced relaxation in aortic rings with or without PVAT. EDR without PVAT was modestly decreased in AE2KO with HFHSD compared with wild type mice (WT) with HFHSD. Aortic rings with PVAT increased EDR in WT with ND. PVAT modestly decreased EDR in WT with HFHSD and mostly eliminated EDR in AE2KO with HFHSD. To assess the contraction factors released from PVAT, the solutions incubated with PVAT (SIP) were transferred to the normal aortic rings. SIP from WT with HFHSD mildly increased vascular tone and SIP from AE2KO with HFHSD further increased it. Tempol, which was superoxide scavenger, restored endothelial dysfunction with PVAT and suppressed the contraction with SIP from AE2KO with HFHSD. Fluorescence intensity of dihydroethidium stain of aorta and PVAT, which indicated that aortic and adipose superoxide production were elevated in AE2KO with HFHSD, which were mostly eliminated with tempol. Conclusions Adipose ERK2 selectively modulated differentiation in SF, suppressed the aortic oxidative stress and protected from endothelial dysfunction in obese. Moreover, adipose ERK2 suppressed the hypertrophy, inflammation, and oxidative stress of PVAT in obese. The oxidative stress with the inflammation in PVAT released vasoconstriction factors, which contributed to endothelial dysfunction in obese mice. Figure 1 Funding Acknowledgement Type of funding source: None

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Endothelial dysfunction in adipose triglyceride lipase deficiency: role of perivascular adipose tissue

BMC Pharmacology and Toxicology ◽

10.1186/2050-6511-14-s1-p45 ◽

2013 ◽

Vol 14 (S1) ◽

Author(s):

Marion Mussbacher ◽

Karoline Pail ◽

Gerald Wölkart ◽

Günter Hämmerle ◽

Alois Lametschwandtner ◽

...

Keyword(s):

Adipose Tissue ◽

Endothelial Dysfunction ◽

Adipose Triglyceride Lipase ◽

Perivascular Adipose Tissue ◽

Triglyceride Lipase

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Tackle inflammation associated with endothelial dysfunction in type 2 diabetes: Role of perivascular adipose tissue

Atherosclerosis ◽

10.1016/j.atherosclerosis.2020.10.418 ◽

2020 ◽

Vol 315 ◽

pp. e135

Author(s):

L. Azul ◽

M. Queiroz ◽

A. Leandro ◽

R. Seiça ◽

C.M. Sena

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Endothelial Dysfunction ◽

Perivascular Adipose Tissue

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Association of Gut Hormones and Microbiota with Vascular Dysfunction in Obesity

Nutrients ◽

10.3390/nu13020613 ◽

2021 ◽

Vol 13 (2) ◽

pp. 613

Author(s):

Valentina Rovella ◽

Giuseppe Rodia ◽

Francesca Di Daniele ◽

Carmine Cardillo ◽

Umberto Campia ◽

...

Keyword(s):

Adipose Tissue ◽

Endothelial Dysfunction ◽

Gut Microbiota ◽

Vascular Function ◽

Vascular Reactivity ◽

Metabolic Diseases ◽

Gut Hormones ◽

Perivascular Adipose Tissue ◽

Complex Mechanisms

In the past few decades, obesity has reached pandemic proportions. Obesity is among the main risk factors for cardiovascular diseases, since chronic fat accumulation leads to dysfunction in vascular endothelium and to a precocious arterial stiffness. So far, not all the mechanisms linking adipose tissue and vascular reactivity have been explained. Recently, novel findings reported interesting pathological link between endothelial dysfunction with gut hormones and gut microbiota and energy homeostasis. These findings suggest an active role of gut secretome in regulating the mediators of vascular function, such as nitric oxide (NO) and endothelin-1 (ET-1) that need to be further investigated. Moreover, a central role of brain has been suggested as a main player in the regulation of the different factors and hormones beyond these complex mechanisms. The aim of the present review is to discuss the state of the art in this field, by focusing on the processes leading to endothelial dysfunction mediated by obesity and metabolic diseases, such as insulin resistance. The role of perivascular adipose tissue (PVAT), gut hormones, gut microbiota dysbiosis, and the CNS function in controlling satiety have been considered. Further understanding the crosstalk between these complex mechanisms will allow us to better design novel strategies for the prevention of obesity and its complications.

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An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity

International Journal of Molecular Sciences ◽

10.3390/ijms22157975 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7975

Author(s):

Saioa Gómez-Zorita ◽

Iñaki Milton-Laskibar ◽

Laura García-Arellano ◽

Marcela González ◽

María P. Portillo

Keyword(s):

Adipose Tissue ◽

Protective Role ◽

Inflammatory Factors ◽

Current Evidence ◽

Disease Outcomes ◽

Lower Activation ◽

Two Factors ◽

Obese Subjects ◽

Ace2 Gene

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

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Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour

International Journal of Molecular Sciences ◽

10.3390/ijms22115560 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5560

Author(s):

Alejandro Álvarez-Artime ◽

Belén García-Soler ◽

Rosa María Sainz ◽

Juan Carlos Mayo

Keyword(s):

Prostate Cancer ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Tumor Development ◽

Cell Types ◽

Protective Role ◽

Bioactive Molecules ◽

Brown Adipose ◽

Endocrine Organs

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.

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