Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.
The Lydia Becker Institute of Immunology & Inflammation, University of Manchester, Manchester, UK.
Cardiovasc Drugs Ther. 2021 Dec;35(6):1291-1304. doi: 10.1007/s10557-020-07136-0. Epub 2021 Mar 9.
Perivascular 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 β-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.
Vascular 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 β-adrenoceptors, OCT3 and tumour necrosis factor-α (TNFα) in PVAT.
High 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 β-adrenoceptor activation. Moreover, adiponectin no longer exerts vasodilation. Additionally, exercise reversed PVAT dysfunction in obesity by reducing inflammation of PVAT and increasing β-adrenoceptor and OCT3 expression, which were downregulated in obesity. Furthermore, the vasodilator effects of adiponectin were restored.
Loss 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.
血管周围脂肪组织（PVAT）发挥抗收缩作用，这对于调节血管张力至关重要。这种作用是通过交感神经刺激 PVAT 来介导的，其机制涉及通过有机阳离子转运体 3（OCT3）摄取去甲肾上腺素和β-肾上腺素能受体介导脂联素释放。在肥胖中，自主神经功能障碍发生，这可能导致 PVAT 功能丧失和随后的血管疾病。因此，我们研究了肥胖 PVAT 的异常，以及运动恢复功能的潜力。
在存在药理学工具的情况下，通过离体实验评估了肥胖和运动肥胖小鼠±PVAT 血管对电刺激（EFS）的血管收缩性。免疫组织化学用于检测 PVAT 中β-肾上腺素能受体、OCT3 和肿瘤坏死因子-α（TNFα）表达的变化。
高脂肪喂养诱导高血压、高血糖和高胰岛素血症，运动可独立于体重减轻而逆转。肥胖导致 PVAT 抗收缩作用丧失，无法通过β-肾上腺素能受体激活恢复。此外，脂联素不再发挥血管舒张作用。此外，运动通过减少 PVAT 炎症和增加β-肾上腺素能受体和 OCT3 表达来逆转肥胖中的 PVAT 功能障碍，肥胖会导致这些表达下调。此外，脂联素的血管舒张作用得到恢复。
肥胖中中性介导的 PVAT 抗收缩功能丧失将导致高血压和 II 型糖尿病的发展。运动训练将恢复功能并治疗肥胖的血管并发症。
