scholarly journals Restoring Perivascular Adipose Tissue Function in Obesity Using Exercise

2021 ◽  
Author(s):  
Sophie N Saxton ◽  
Lauren K Toms ◽  
Robert G Aldous ◽  
Sarah B Withers ◽  
Jacqueline Ohanian ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Contractile Function ◽  
Ex Vivo ◽  
Vascular Complications ◽  
Electrical Field Stimulation ◽  
Organic Cation Transporter ◽  
Nervous Stimulation ◽  
Perivascular Adipose Tissue ◽  
Contractile Effect ◽  
Organic Cation Transporter 3

AbstractPurposePerivascular adipose tissue (PVAT) exerts an anti-contractile effect which is vital in regulating vascular tone. This effect is mediated via sympathetic nervous stimulation of PVAT by a mechanism which involves noradrenaline uptake through organic cation transporter 3 (OCT3) and β3-adrenoceptor-mediated adiponectin release. In obesity, autonomic dysfunction occurs, which may result in a loss of PVAT function and subsequent vascular disease. Accordingly, we have investigated abnormalities in obese PVAT, and the potential for exercise in restoring function.MethodsVascular contractility to electrical field stimulation (EFS) was assessed ex vivo in the presence of pharmacological tools in ±PVAT vessels from obese and exercised obese mice. Immunohistochemistry was used to detect changes in expression of β3-adrenoceptors, OCT3 and tumour necrosis factor-α (TNFα) in PVAT.ResultsHigh fat feeding induced hypertension, hyperglycaemia, and hyperinsulinaemia, which was reversed using exercise, independent of weight loss. Obesity induced a loss of the PVAT anti-contractile effect, which could not be restored via β3-adrenoceptor activation. Moreover, adiponectin no longer exerts vasodilation. Additionally, exercise reversed PVAT dysfunction in obesity by reducing inflammation of PVAT and increasing β3-adrenoceptor and OCT3 expression, which were downregulated in obesity. Furthermore, the vasodilator effects of adiponectin were restored.ConclusionLoss of neutrally mediated PVAT anti-contractile function in obesity will contribute to the development of hypertension and type II diabetes. Exercise training will restore function and treat the vascular complications of obesity.

Abstract 333: Existence of Functional Norepinephrine Transport in Perivascular Adipose Tissue

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Nadia Ayala-Lopez ◽  
Robert Burnett ◽  
Janice M Thompson ◽  
Stephanie W Watts
Keyword(s):  
Blood Vessel ◽  
Contractile Function ◽  
Organic Cation Transporter ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Perivascular Adipose Tissue ◽  
Healthy State ◽  
Health And Disease ◽  
Organic Cation Transporter 3 ◽  
Beta 2 Microglobulin

Perivascular Tissue (PVAT) is a recent focus of studies for its regulation of blood vessel tone. Contraction to norepinephrine (NE) is reduced by PVAT through mechanisms not entirely clear. Loss of this anti-contractile function of PVAT occurs in obesity-related hypertension. We hypothesized that PVAT can remove NE from the blood vessel environment through transporters and reduce NE induced contraction in health. RT-PCR of mesenteric PVAT was positive for norepinephrine transporter (NET; Ct=33.2±1.4) and serotonin transporter (SERT; Ct=31.9±0.9) relative to beta-2-microglobulin. To study NE uptake in the healthy state, mesenteric and aortic PVAT from the male Sprague Dawley rat was incubated with 10 μM NE after pre-incubation with an inhibitor of transport (10 μM desipramine to inhibit NET and SERT, 100 μM corticosterone to inhibit organic cation transporter 3) or vehicle and quantified by HPLC for NE. Desipramine plus corticosterone inhibited NE uptake in mesenteric PVAT (figure) but desipramine (410.5±80.8 ng/g vs. 414.4±67.0 ng/g NE only; n=8) or corticosterone (225.0±26.1 ng/g vs. 319.2±35.9 ng/g NE only; n=5) alone did not, indicating a robust uptake capacity. In aortic PVAT, NE uptake was not inhibited by desipramine plus corticosterone (figure), desipramine (1763.5±460.8 ng/g vs. 1702.7±298.4 ng/g NE only; n=6), or corticosterone (1085.8±205.3 ng/g vs. 2245.8±506.8 ng/g NE only; n=4). Protein staining revealed bands positive for NET in mesenteric PVAT by Western blot. Taken together, we found that PVAT is a reservoir of NE that can remove NE from the blood vessel environment, an important finding to understand vasculature-PVAT interactions in health and disease.

scholarly journals Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue

2015 ◽  
Vol 309 (11) ◽  
pp. H1904-H1914 ◽  
Author(s):  
Nadia Ayala-Lopez ◽  
William F. Jackson ◽  
Robert Burnett ◽  
James N. Wilson ◽  
Janice M. Thompson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Confocal Imaging ◽  
Uptake System ◽  
Sprague Dawley ◽  
Uptake Mechanism ◽  
Fluorescent Substrate ◽  
Perivascular Adipose Tissue ◽  
Organic Cation Transporter 3

Perivascular adipose tissue (PVAT) reduces vasoconstriction to norepinephrine (NE). A mechanism by which PVAT could function to reduce vascular contraction is by decreasing the amount of NE to which the vessel is exposed. PVATs from male Sprague-Dawley rats were used to test the hypothesis that PVAT has a NE uptake mechanism. NE was detected by HPLC in mesenteric PVAT and isolated adipocytes. Uptake of NE (10 μM) in mesenteric PVAT was reduced by the NE transporter (NET) inhibitor nisoxetine (1 μM, 73.68 ± 7.62%, all values reported as percentages of vehicle), the 5-hydroxytryptamine transporter (SERT) inhibitor citalopram (100 nM) with the organic cation transporter 3 (OCT3) inhibitor corticosterone (100 μM, 56.18 ± 5.21%), and the NET inhibitor desipramine (10 μM) with corticosterone (100 μM, 61.18 ± 6.82%). Aortic PVAT NE uptake was reduced by corticosterone (100 μM, 53.01 ± 10.96%). Confocal imaging of mesenteric PVAT stained with 4-[4-(dimethylamino)-styrl]- N-methylpyridinium iodide (ASP+), a fluorescent substrate of cationic transporters, detected ASP+ uptake into adipocytes. ASP+ (2 μM) uptake was reduced by citalopram (100 nM, 66.68 ± 6.43%), corticosterone (100 μM, 43.49 ± 10.17%), nisoxetine (100 nM, 84.12 ± 4.24%), citalopram with corticosterone (100 nM and 100 μM, respectively, 35.75 ± 4.21%), and desipramine with corticosterone (10 and 100 μM, respectively, 50.47 ± 5.78%). NET protein was not detected in mesenteric PVAT adipocytes. Expression of Slc22a3 (OCT3 gene) mRNA and protein in PVAT adipocytes was detected by RT-PCR and immunocytochemistry, respectively. These end points support the presence of a transporter-mediated NE uptake system within PVAT with a potential mediator being OCT3.

Attenuation of the anti-contractile effect of cooling in the rat aorta by perivascular adipose tissue

2017 ◽  
Vol 37 (4) ◽  
pp. 52-60
Author(s):  
Y. Rafique ◽  
M. AlBader ◽  
M. Oriowo
Keyword(s):  
Adipose Tissue ◽  
Rat Aorta ◽  
Perivascular Adipose Tissue ◽  
Contractile Effect

scholarly journals Organic cation transporter 3 (Oct3) is a distinct catecholamines clearance route in adipocytes mediating the beiging of white adipose tissue

PLoS Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
pp. e2006571 ◽  
Author(s):  
Wenxin Song ◽  
Qi Luo ◽  
Yuping Zhang ◽  
Linkang Zhou ◽  
Ye Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporter 3

Reduced anti-contractile effect of perivascular adipose tissue on mesenteric small arteries from spontaneously hypertensive rats: Role of Kv7 channels

2013 ◽  
Vol 698 (1-3) ◽  
pp. 310-315 ◽  
Author(s):  
Rui Li ◽  
Ingrid Andersen ◽  
Josefin Aleke ◽  
Veronika Golubinskaya ◽  
Helena Gustafsson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Perivascular Adipose Tissue ◽  
Spontaneously Hypertensive ◽  
Small Arteries ◽  
Kv7 Channels ◽  
Contractile Effect

scholarly journals Anti‐Contractile Effect of Perivascular Adipose Tissue in Pregnant Rat Aorta

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Mabayoje Oriowo ◽  
Aishah Al‐Jarallah
Keyword(s):  
Adipose Tissue ◽  
Rat Aorta ◽  
Perivascular Adipose Tissue ◽  
Pregnant Rat ◽  
Contractile Effect

Abstract 1041: Endovascular Injury Affects Adipocytokine Profile Of The Periadventitial Adipose Tissue

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Minoru Takaoka ◽  
Masataka Sata ◽  
Ryozo Nagai
Keyword(s):  
Adipose Tissue ◽  
Proinflammatory Cytokines ◽  
Ex Vivo ◽  
Wistar Rat ◽  
Tnf Alpha ◽  
Pcr Analysis ◽  
Down Regulation ◽  
Perivascular Adipose Tissue ◽  
Anti Inflammatory ◽  
Pai 1

Background: Adipose tissue secretes not only proinflammatory cytokines but also anti-inflammatory cytokines such as adiponectin. Arteries are surrounded by abundant periadventitial fat tissues, which have been suggested to play a role in maintenance of vascular homeostasis. Here, we investigated whether endovascular injury affects the profile of adipocytokines expressed by perivascular adipose tissue (PAT). Methods and Results: First, the femoral artery of C57BL/6 mice was overstretched by insertion of a large wire. Real-time PCR analysis revealed that wire injury markedly down-regulated adiponectin expression (0.64±0.09 fold, p<0.01) and up-regulated expression of proinflammatory cytokines, TNF alpha, IL-6, PAI-1, and MCP-1 (p<0.01) 1 day after overstretch within PAT. Neutrophils and macrophages accumulated in the adventitia surrounding the injury site at 1 day after the injury. Inflammation was associated temporally with the expression of mRNAs encoding inflammatory adipocytokines. Second, the iliac artery of Wistar rats was dilated percutaneously with a balloon for 1 minute. There were up-regulation of proinflammatory cytokines and down-regulation of adiponectin 1 and 3days after endovascular injury within PAT (p<0.05). Third, abdominal aortas removed from Wistar rat with PAT were dilated with a balloon PTCA catheter for 1 minute ex vivo. After stretching, aortas with PAT were cultured for 6 hours, and we observed increased synthesis of proinflammatory cytokines and decreased synthesis of adiponectin within PAT (p<0.05). Fourth, the stimulation of TNF alpha, which markedly increased in injured arteries, caused significant down-regulation of adiponectin expression and up-regulation of IL-6, PAI-1, and MCP-1 in 3T3L1-derived adipocytes (p<0.01). Conclusions: Angioplasty may induce the changes of perivascular cytokines expression. The accumulation of neutrophils and macrophages at PAT in injured arteries and/or increased proinflammatory expression of injured vascular arteries may reflect these proinflammatory activities of PAT. Increased proinflammatory cytokines and decreased anti-inflammatory cytokine adiponectin in PAT possibly may have a role in vascular remodeling following PTCA-mediated vascular injury.

scholarly journals Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats

2016 ◽  
Vol 40 (8) ◽  
pp. 1205-1214 ◽  
Author(s):  
K E Zaborska ◽  
M Wareing ◽  
G Edwards ◽  
C Austin
Keyword(s):  
Adipose Tissue ◽  
Maternal Obesity ◽  
Later Life ◽  
Independent Effect ◽  
Sprague Dawley ◽  
Response Curves ◽  
Perivascular Adipose Tissue ◽  
Contractile Effect ◽  
Sprague Dawley Rats ◽  
Pregnancy And Lactation

Abstract Rationale: Maternal obesity pre-programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature, which is reduced in hypertension and obesity. Objective: The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life. Methods: Female Sprague–Dawley rats were fed a diet containing 10% (control) or 45% fat (high fat diet, HFD) for 12 weeks prior to mating and during pregnancy and lactation. Male offspring were killed at 12 or 24 weeks of age and tension in PVAT-intact or -denuded mesenteric artery segments was measured isometrically. Concentration–response curves were constructed to U46619 and norepinephrine. Results: Only 24-week-old HFD offspring were hypertensive (P<0.0001), although the anti-contractile effect of PVAT was lost in vessels from HFD offspring of each age. Inhibition of nitric oxide (NO) synthase with 100 μM l-NMMA attenuated the anti-contractile effect of PVAT and increased contractility of PVAT-denuded arteries (P<0.05, P<0.0001). The increase in contraction was smaller in PVAT-intact than PVAT-denuded vessels from 12-week-old HFD offspring, suggesting decreased PVAT-derived NO and release of a contractile factor (P<0.07). An additional, NO-independent effect of PVAT was evident only in norepinephrine-contracted vessels. Activation of AMP-activated kinase (with 10 μM A769662) was anti-contractile in PVAT-denuded (P<0.0001) and -intact (P<0.01) vessels and was due solely to NO in controls; the AMPK effect was similar in HFD offspring vessels (P<0.001 and P<0.01, respectively) but was partially NO-independent. Conclusions: The diminished anti-contractile effects of PVAT in offspring of HFD dams are primarily due to release of a PVAT-derived contractile factor and reduced NO bioavailability.

scholarly journals JNK2 in myeloid cells impairs insulin’s vasodilator effects in muscle during early obesity development through perivascular adipose tissue dysfunction

2019 ◽  
Vol 317 (2) ◽  
pp. H364-H374
Author(s):  
Rick I. Meijer ◽  
Femke P. M. Hoevenaars ◽  
Erik H. Serné ◽  
John S. Yudkin ◽  
Tom J. A. Kokhuis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Ex Vivo ◽  
Myeloid Cells ◽  
Inflammatory Cells ◽  
Western Diet ◽  
Perivascular Adipose Tissue ◽  
Muscle Perfusion

Reduced vasodilator properties of insulin in obesity are caused by changes in perivascular adipose tissue and contribute to microvascular dysfunction in skeletal muscle. The causes of this dysfunction are unknown. The effects of a short-term Western diet on JNK2-expressing cells in perivascular adipose tissue (PVAT) on insulin-induced vasodilation and perfusion of skeletal muscle were assessed. In vivo, 2 wk of Western diet (WD) reduced whole body insulin sensitivity and insulin-stimulated muscle perfusion, determined using contrast ultrasonography during the hyperinsulinemic clamp. Ex vivo, WD triggered accumulation of PVAT in skeletal muscle and blunted its ability to facilitate insulin-induced vasodilation. Labeling of myeloid cells with green fluorescent protein identified bone marrow as a source of PVAT in muscle. To study whether JNK2-expressing inflammatory cells from bone marrow were involved, we transplanted JNK2−/− bone marrow to WT mice. Deletion of JNK2 in bone marrow rescued the vasodilator phenotype of PVAT during WD exposure. JNK2 deletion in myeloid cells prevented the WD-induced increase in F4/80 expression. Even though WD and JNK2 deletion resulted in specific changes in gene expression of PVAT; epididymal and subcutaneous adipose tissue; expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, or protein inhibitor of STAT1 was not affected. In conclusion, short-term Western diet triggers infiltration of JNK2-positive myeloid cells into PVAT, resulting in PVAT dysfunction, nonclassical inflammation, and loss of insulin-induced vasodilatation in vivo and ex vivo. NEW & NOTEWORTHY We demonstrate that in the earliest phase of weight gain, changes in perivascular adipose tissue in muscle impair insulin-stimulated muscle perfusion. The hallmark of these changes is infiltration by inflammatory cells. Deletion of JNK2 from the bone marrow restores the function of perivascular adipose tissue to enhance insulin’s vasodilator effects in muscle, showing that the bone marrow contributes to regulation of muscle perfusion.

scholarly journals Erratum: Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats

2017 ◽  
Vol 41 (6) ◽  
pp. 997-997 ◽  
Author(s):  
K E Zaborska ◽  
M Wareing ◽  
G Edwards ◽  
C Austin
Keyword(s):  
Adipose Tissue ◽  
Perivascular Adipose Tissue ◽  
Contractile Effect ◽  
Obese Rats
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