University of São Paulo (USP), Ribeirão Preto, Brazil.
J Pineal Res. 2021 Mar;70(2):e12710. doi: 10.1111/jpi.12710. Epub 2020 Dec 26.
Perivascular adipose tissue (PVAT) undergoes functional changes in obesity. Increased oxidative stress is a central mechanism whereby obesity induces loss of the anticontractile effect of PVAT. Melatonin is an antioxidant that displays vasoprotective action in cardiovascular disease. Here, we sought to investigate whether melatonin would restore the anticontractile effect of periaortic PVAT in obesity. Male Wistar Hannover rats were treated for 10 weeks with a high-calorie diet. Melatonin (5 mg/kg/d, p.o., gavage) was administered for 2 weeks. Functional findings showed that obesity-induced loss of the anticontractile effect of PVAT and treatment with melatonin reversed this response. Tiron [a scavenger of superoxide anion (O )] restored the anticontractile effect of PVAT in aortas from obese rats, suggesting a role for reactive oxygen species (ROS) in such response. Decreased superoxide dismutase (SOD) activity and augmented levels of ROS were detected in periaortic PVAT from obese rats. These responses were accompanied by decreased levels of nitric oxide (NO) in PVAT. Treatment with melatonin restored SOD activity, decreased ROS levels, and increased NO bioavailability in PVAT from obese rats. Here, we first reported the beneficial effects of melatonin in periaortic PVAT in obesity. Melatonin reversed the adverse effects of obesity in PVAT that included overproduction of ROS, reduced SOD activity, and decreased bioavailability of NO. Therefore, PVAT may constitute an important target for the treatment of obesity-induced vascular dysfunction and melatonin emerges as a potential tool in the management of the vascular complications induced by obesity.
血管周脂肪组织（PVAT）在肥胖中发生功能变化。氧化应激增加是肥胖导致 PVAT 抗收缩作用丧失的核心机制。褪黑素是一种抗氧化剂，在心血管疾病中具有血管保护作用。在这里，我们试图研究褪黑素是否会恢复肥胖中主动脉旁 PVAT 的抗收缩作用。雄性 Wistar 汉诺威大鼠用高热量饮食治疗 10 周。褪黑素（5mg/kg/d，口服，灌胃）给药 2 周。功能发现表明，肥胖诱导的 PVAT 抗收缩作用丧失，褪黑素治疗逆转了这种反应。Tiron（超氧阴离子 (O )的清除剂）恢复了肥胖大鼠主动脉中 PVAT 的抗收缩作用，表明活性氧 (ROS) 在这种反应中起作用。肥胖大鼠血管周 PVAT 中超氧化物歧化酶 (SOD)活性降低，ROS 水平升高。这些反应伴随着 PVAT 中一氧化氮 (NO)水平降低。褪黑素治疗恢复了肥胖大鼠 PVAT 中的 SOD 活性，降低了 ROS 水平，并增加了 NO 的生物利用度。在这里，我们首次报道了褪黑素在肥胖大鼠血管周 PVAT 中的有益作用。褪黑素逆转了肥胖对 PVAT 的不利影响，包括 ROS 过度产生、SOD 活性降低和 NO 生物利用度降低。因此，PVAT 可能成为肥胖引起的血管功能障碍治疗的重要靶点，而褪黑素作为肥胖引起的血管并发症治疗的潜在工具出现。
