Abstract

Background: The mechanisms underlying the perivascular adipose tissue (PVAT) dysfunction in obesity are closely related to inflammation and oxidative stress. The present study aimed to investigate the effects of aerobic exercise training on PVAT-induced endothelial dysfunction of thoracic aorta of obese mice.Methods: Male mice C57BL6/JUnib (6–7 weeks) were divided into: sedentary (c-SD), trained (c-TR), obese sedentary (o-SD), and obese trained (o-TR). Obesity was induced by 16 weeks of high-fat diet and exercise training of moderate intensity started after 8 weeks of protocol and was performed on a treadmill, 5 days/week, for more 8 weeks, 60 min per session. The vascular responsiveness was performed in thoracic aorta in the absence (PVAT−) or in the presence (PVAT+) of PVAT. We analyzed circulatory parameters, protein expression, vascular nitric oxide (NO) production, and reactive oxygen species (ROS) in PVAT.Results: The maximal responses to acetylcholine (ACh) were reduced in PVAT+ compared with PVAT− rings in the o-SD group, accompanied by an increase in circulating glucose, insulin, resistin, leptin, and TNF-α. Additionally, the protein expression of iNOS and generation of ROS were increased in PVAT and production of vascular NO was reduced in the o-SD group compared with c-SD. In the o-TR group, the relaxation response to ACh was completely restored and the circulatory TNF-α, iNOS protein expression, and ROS were normalized with increased expression of Mn-SOD in PVAT, resulting in enhanced vascular NO production.Conclusion: The PVAT-induced endothelial dysfunction in thoracic aorta of obese mice, associated with circulatory inflammation and oxidative stress. Aerobic exercise training upregulated the anti-oxidant expression and decreased PVAT oxidative stress with beneficial impact on endothelium-dependent relaxation.

Highlights

  • The unique and specialized paracrine/endocrine function of perivascular adipose tissue (PVAT) to regulate vascular responsiveness has been recently identified

  • Other studies unveiled an association of endothelial dysfunction and PVAT in obese animals (Ketonen et al, 2010; Xia and Li, 2017; DeVallance et al, 2018), showing a potential adipose dysfunction of PVAT and a complex mechanism involving inflammation, increased production of reactive oxygen species (ROS), and alterations in endothelial nitric oxide synthase pathways (Bailey-Downs et al, 2013; Xia et al, 2016)

  • We verified an improvement in physical performance as assessed by total time, total distance, and maximal speed in the c-TR and obese trained (o-TR) group when compared with the c-SD and obese sedentary (o-SD) groups, respectively

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Summary

Introduction

The unique and specialized paracrine/endocrine function of perivascular adipose tissue (PVAT) to regulate vascular responsiveness has been recently identified. Other studies unveiled an association of endothelial dysfunction and PVAT in obese animals (Ketonen et al, 2010; Xia and Li, 2017; DeVallance et al, 2018), showing a potential adipose dysfunction of PVAT and a complex mechanism involving inflammation, increased production of reactive oxygen species (ROS), and alterations in endothelial nitric oxide synthase (eNOS) pathways (Bailey-Downs et al, 2013; Xia et al, 2016). Obesity has diverse adverse effects on cardiovascular system (Montero et al, 2012) In this condition, the adipose tissue becomes dysfunctional and shifts toward a pro-inflammatory and pro-oxidative state linked to endothelial dysfunction (de Mello et al, 2018). The present study aimed to investigate the effects of aerobic exercise training on PVAT-induced endothelial dysfunction of thoracic aorta of obese mice

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