Silva Josiane F, Correa Izabella C, Diniz Thiago F, Lima Paulo M, Santos Roger L, Cortes Steyner F, Coimbra Cândido C, Lemos Virginia S
Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais Belo Horizonte, Brazil.
Department of Physiological Science, Universidade Federal do Espírito Santo Espírito Santo, Brazil.
Front Physiol. 2016 Sep 7;7:386. doi: 10.3389/fphys.2016.00386. eCollection 2016.
The understanding of obsesity-related vascular dysfunction remains controversial mainly because of the diseases associated with vascular injury. Exercise training is known to prevent vascular dysfunction. Using an obesity model without comorbidities, we aimed at investigating the underlying mechanism of vascular dysfunction and how exercise interferes with this process.
High-sugar diet was used to induce obesity in mice. Exercise training was performed 5 days/week. Body weight, energy intake, and adipose tissues were assessed; blood metabolic and hormonal parameters were determined; and serum TNFα was measured. Blood pressure and heart rate were assessed by plethysmography. Changes in aortic isometric tension were recorded on myograph. Western blot was used to analyze protein expression. Nitric oxide (NO) was evaluated using fluorescence microscopy. Antisense oligodeoxynucleotides were used for inducible nitric oxide synthase isoform (iNOS) knockdown.
Body weight, fat mass, total cholesterol, low-density lipoprotein cholesterol fraction, insulin, and leptin were higher in the sedentary obese group (SD) than in the sedentary control animals (SS). Exercise training prevented these changes. No difference in glucose tolerance, insulin sensitivity, blood pressure, and heart rate was found. Decreased vascular relaxation and reduced endothelial nitric oxide synthase (eNOS) functioning in the SD group were prevented by exercise. Contractile response to phenylephrine was decreased in the aortas of the wild SD mice, compared with that of the SS group; however, no alteration was noted in the SD iNOS(-/-) animals. The decreased contractility was endothelium-dependent, and was reverted by iNOS inhibition or iNOS silencing. The aortas from the SD group showed increased basal NO production, serum TNFα, TNF receptor-1, and phospho-IκB. Exercise training attenuated iNOS-dependent reduction in contractile response in high-sugar diet-fed animals, decreased iNOS expression, and increased eNOS expression.
Obesity caused endothelium dysfunction, TNFα, and iNOS pathway up-regulation, decreasing vascular contractility in the obese animals. Exercise training was an effective therapy to control iNOS-dependent NO production and to preserve endothelial function in obese individuals.
由于与血管损伤相关的疾病，对肥胖相关血管功能障碍的理解仍存在争议。已知运动训练可预防血管功能障碍。我们使用无合并症的肥胖模型，旨在研究血管功能障碍的潜在机制以及运动如何干扰这一过程。
用高糖饮食诱导小鼠肥胖。每周进行5天运动训练。评估体重、能量摄入和脂肪组织；测定血液代谢和激素参数；测量血清TNFα。通过体积描记法评估血压和心率。在肌动描记器上记录主动脉等长张力的变化。用蛋白质印迹法分析蛋白质表达。使用荧光显微镜评估一氧化氮（NO）。用反义寡脱氧核苷酸敲低诱导型一氧化氮合酶同工型（iNOS）。
久坐肥胖组（SD）的体重、脂肪量、总胆固醇、低密度脂蛋白胆固醇组分、胰岛素和瘦素高于久坐对照动物（SS）。运动训练可预防这些变化。未发现葡萄糖耐量、胰岛素敏感性、血压和心率有差异。运动可预防SD组血管舒张减少和内皮型一氧化氮合酶（eNOS）功能降低。与SS组相比，野生SD小鼠主动脉对去氧肾上腺素的收缩反应降低；然而，SD iNOS（-/-）动物未观察到改变。收缩性降低是内皮依赖性的，可通过iNOS抑制或iNOS沉默恢复。SD组的主动脉显示基础NO产生增加、血清TNFα、TNF受体-1和磷酸化IκB增加。运动训练减弱了高糖饮食喂养动物中iNOS依赖性收缩反应的降低，降低了iNOS表达，并增加了eNOS表达。
肥胖导致内皮功能障碍、TNFα和iNOS途径上调，降低了肥胖动物的血管收缩性。运动训练是控制肥胖个体中iNOS依赖性NO产生和维持内皮功能的有效疗法。
