Sousa Andressa S, Sponton Amanda C S, Trifone César B, Delbin Maria A
Laboratory of Vascular Biology, Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.
Front Physiol. 2019 Aug 16;10:1009. doi: 10.3389/fphys.2019.01009. eCollection 2019.
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. 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. 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. 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.
肥胖状态下血管周围脂肪组织(PVAT)功能障碍的潜在机制与炎症和氧化应激密切相关。本研究旨在探讨有氧运动训练对肥胖小鼠胸主动脉PVAT诱导的内皮功能障碍的影响。将雄性C57BL6/JUnib小鼠(6 - 7周龄)分为:久坐组(c - SD)、训练组(c - TR)、肥胖久坐组(o - SD)和肥胖训练组(o - TR)。通过16周的高脂饮食诱导肥胖,在方案实施8周后开始中等强度的运动训练,在跑步机上进行,每周5天,持续8周,每次60分钟。在不存在PVAT(PVAT - )或存在PVAT(PVAT + )的情况下,对胸主动脉进行血管反应性检测。我们分析了循环参数、蛋白表达、血管一氧化氮(NO)生成以及PVAT中的活性氧(ROS)。与o - SD组的PVAT - 环相比,PVAT + 环对乙酰胆碱(ACh)的最大反应降低,同时循环中的葡萄糖、胰岛素、抵抗素、瘦素和TNF - α增加。此外,与c - SD组相比,o - SD组PVAT中诱导型一氧化氮合酶(iNOS)的蛋白表达和ROS生成增加,血管NO生成减少。在o - TR组中,对ACh的舒张反应完全恢复,循环中的TNF - α、iNOS蛋白表达和ROS恢复正常,PVAT中锰超氧化物歧化酶(Mn - SOD)表达增加,导致血管NO生成增强。肥胖小鼠胸主动脉中PVAT诱导的内皮功能障碍与循环炎症和氧化应激有关。有氧运动训练上调抗氧化剂表达并降低PVAT氧化应激,对内皮依赖性舒张有有益影响。