scholarly journals Association of Gut Hormones and Microbiota with Vascular Dysfunction in Obesity

Nutrients ◽  
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.

Abstract 66: Altered Vascular Reactivity in Mice Overexpressing Adipocyte Mineralocorticoid Receptors - Role of Oxidative Stress and Rho Kinase

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Aurelie Nguyen Dinh Cat ◽  
Glaucia E Callera ◽  
Tayze T Antunes ◽  
Augusto C Montezano ◽  
Ying He ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Tissue Interactions

Aldosterone (aldo) plays a role in obesity and cardiovascular diseases, such as hypertension. We previously demonstrated that adipocyte-derived factors regulate vascular function and vascular smooth muscle cells signaling. Moreover, adipocytes express aldosterone synthase (CYP11B2) and produce aldo. The mineralocorticoid receptor (MR), which is responsible for aldo signaling, is also found in these cells, but its role in regulating adipose tissue interactions with the vasculature is unknown. In this study, we investigated mechanisms whether MR activation in adipocytes regulates vascular reactivity. Conditional transgenic mice that overexpress MR in an adipocyte-specific manner were studied. Vascular reactivity of resistance mesenteric arteries to acetylcholine (Ach), sodium nitroprusside and phenylephrine (Phe), in the absence or presence of fat conditioned medium (Fcm) from control and adipocyte overexpressing MR (MROE) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in MROE or control (Ctr) mice. However, exposure of arteries from control mice to Fcm from MROE mice induces endothelial dysfunction (Ach 10 -6 M: 77.5±9.6% no Fcm vs. 49.8±7.5% Fcm, p<0.05), an effect blocked by N-acetyl-cysteine (an antioxidant) (Ach 10 -6 M: 82.2±6.6%). Resistance arteries from MROE mice had decreased Phe-induced contraction, compared to control mice (Phe 10 -5 M: 2.7±0.2 mN/mm Ctr vs. 1.7±0.2 mN/mm MROE, p<0.05). Rho Kinase activity, which regulates vascular contraction, is decreased in arteries and adipo tissue from MROE (mesenteric arteries, Ctr: 100±16.2% vs. MROE: 31.1±6.1%, arbitrary units, p<0.01; adipose tissue, Ctr: 100±12.6% vs. MROE: 51.3±9.3%, arbitrary units, p<0.01). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, through redox-sensitive pathways and activation of Rho kinase. Our study identifies novel mechanisms linking vascular/adipose tissue biology and aldo/MR activation, which may be particularly important in vascular dysfunction associated with hypertension and hyperaldosteronism.

scholarly journals Potential role of perivascular adipose tissue in modulating atherosclerosis

2020 ◽  
Vol 134 (1) ◽  
pp. 3-13 ◽  
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.

Role of Perivascular Adipose Tissue in Vascular Function

2009 ◽  
pp. 175-186 ◽  
Author(s):  
Maria S. Fernández-Alfonso ◽  
Marta Gil-Ortega ◽  
Beatriz Somoza
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Perivascular Adipose Tissue

scholarly journals Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue

2021 ◽  
Vol 8 ◽  
Author(s):  
Mengyu Wang ◽  
Junhui Xing ◽  
Mengduan Liu ◽  
Mingming Gao ◽  
Yangyang Liu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Vascular Function ◽  
Mesenteric Artery ◽  
Critical Role ◽  
Perivascular Adipose Tissue ◽  
Vascular Homeostasis ◽  
Lipid Droplet Formation ◽  
First Time

Seipin locates in endoplasmic reticulum (ER) and regulates adipogenesis and lipid droplet formation. Deletion of Seipin has been well-demonstrated to cause severe general lipodystrophy, however, its role in maintaining perivascular adipose tissue (PVAT) and vascular homeostasis has not been directly assessed. In the present study, we investigated the role of Seipin in mediating the anticontractile effect of PVAT and vascular function. Seipin expression in PVAT and associated vessels were detected by qPCR and western-blot. Seipin is highly expressed in PVAT, but hardly in vessels. Structural and functional alterations of PVAT and associated vessels were compared between Seipin−/− mice and WT mice. In Seipin−/− mice, aortic and mesenteric PVAT were significantly reduced in mass and adipose-derived relaxing factors (ADRFs) secretion, but increased in macrophage infiltration and ER stress, as compared with those in WT mice. Aortic and mesenteric artery rings from WT and Seipin−/− mice were mounted on a wire myograph. Vasoconstriction and vasodilation were studied in vessels with and without PVAT. WT PVAT augmented relaxation but not Seipin−/− PVAT, which suggest impaired anticontractile function in PVAT of Seipin−/− mice. Thoracic aorta and mesenteric artery from Seipin−/− mice had impaired contractility in response to phenylephrine (PHE) and relaxation to acetylcholine (Ach). In conclusion, Seipin deficiency caused abnormalities in PVAT morphology and vascular functions. Our data demonstrated for the first time that Seipin plays a critical role in maintaining PVAT function and vascular homeostasis.

Abstract 138: Altered Vascular Reactivity in Mice Overexpressing Adipocyte Mineralocorticoid Receptors - Role of Rho Kinase.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Aurelie Nguyen Dinh Cat ◽  
Tayze T Antunes ◽  
Glaucia E Callera ◽  
Augusto C Montezano ◽  
Ying He ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Mesenteric Arteries ◽  
Mineralocorticoid Receptors ◽  
Resistance Arteries ◽  
Brown Adipose

Aldosterone (aldo) plays a role in cardiovascular diseases, including hypertension and obesity. We previously demonstrated that adipocyte-derived factors regulate vascular function and cell signaling in cultured vascular smooth muscle cells. Moreover, adipocytes are able to produce aldo, which influences vascular reactivity. Plasma levels of aldo are positively correlated with obesity and hypertension. However, the pathophysiological role of aldo and mineralocorticoid receptors (MR) in adipose tissue and its interactions with the vasculature remains elusive. In our study, we investigated molecular mechanisms whereby activation of MR, in adipocytes, leads to release of vascular reactive factors and regulation of vascular tone, using a conditional transgenic mouse model that overexpresses MR only in the adipocytes. Vascular reactivity of resistance mesenteric arteries to acetylcholine (Ach), sodium nitroprusside and phenylephrine (Phe), in the absence or presence of fat conditioned medium (Fcm) from control and adipocyte overexpressing MR (DT) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in DT or control mice. However, in the presence of Fcm from DT mice, relaxation to Ach was impaired in control mice (Ach 10 -6 M: 77.5±9.6% no Fcm vs. 49.8±7.5% Fcm, p<0.05), an effect blocked by N-acetyl-cysteine (anti-oxidant) (Ach 10 -6 M: 82.2±6.6%). Resistance arteries from DT mice had decreased Phe-induced contraction, compared to control mice (Phe 10 -5 M: 2.7±0.2 mN/mm CT vs. 1.7±0.2 mN/mm DT, p<0.05). Phosphorylation of ezrin, a marker of Rho kinase activation, measured by immunoblotting, was decreased in white and brown adipose tissues of DT (CT: 3.1±0.7 vs. DT: 0.6±0.1, arbitrary units, p<0.05). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, and may be involved in vascular oxidative stress. MR in adipocytes is also important to the anti-contractile properties of the adipose tissue through downregulation of Rho kinase signaling. Our study identiy novel mechanisms linking vascular and adipose biology through adipocyte MRs.

Role of perivascular adipose tissue in endothelial dysfunction of adipose triglyceride lipase-deficient mice

Nitric Oxide ◽  
2012 ◽  
Vol 27 ◽  
pp. S21
Author(s):  
Karoline Dörffel ◽  
Sarah Winkler ◽  
Günter Hämmerle ◽  
Rudolf Zechner ◽  
Alois Lametschwandtner ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Adipose Triglyceride Lipase ◽  
Perivascular Adipose Tissue ◽  
Triglyceride Lipase ◽  
Deficient Mice

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

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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