Perivascular adipose tissue and microvascular endothelial dysfunction in obese mice: Beneficial effects of aerobic exercise in adiponectin receptor (AdipoR1) and peNOSSer1177.

In the present study, we aim to investigate the effects of aerobic physical training on perivascular adipose tissue (PVAT)-induced microvascular dysfunction of the femoral artery in obese mice. Microvascular reactivity was evaluated in control sedentary (c-SD), obese sedentary (o-SD) and obese trained (o-TR) male mice (C57BL6/JUnib), in the absence (PVAT-) or the presence (PVAT+) of femoral artery PVAT. We also analyzed protein expression, vascular nitric oxide (NO) production and reactive oxygen species (ROS) generation in PVAT. The blood glucose, triglycerides and total cholesterol levels were increased in the o-SD group, when compared with the c-SD group. The maximal responses and the potency to acetylcholine (ACh) were decreased in PVAT+ compared with PVAT- rings in the o-SD group, accompanied by a decrease in vascular protein expression of peNOSSer1177 , Cu/Zn-SOD, leptin receptor (Ob-R) and adiponectin receptor (AdipoR1). The protein expression of leptin increased and that of adiponectin decreased in PVAT. Additionally, vascular NO production was reduced and ROS generation was enhanced in PVAT in the o-SD group. Aerobic exercise training was effective for normalizing ACh relaxation response, vascular NO production and ROS generation in the o-TR group. It partially re-established the vascular protein expression of peNOSSer1177 and the PVAT leptin; normalized the vascular Cu/Zn-SOD and AdipoR1 protein expressions. In obese sedentary mice, the presence of PVAT is involved in the process of microvascular dysfunction of the femoral artery in a pathway associated with increased inflammation and ROS generation. The aerobic exercise training normalized the vascular response, the NO production and/or bioavailability and oxidative stress, with improved vascular expressions of Cu/Zn-SOD, peNOSser1177 , and AdipoR1.

Aerobic Exercise Training Prevents Perivascular Adipose Tissue-Induced Endothelial Dysfunction in Thoracic Aorta of Obese Mice.

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.

Anti-contractile effects of perivascular adipose tissue in thoracic aorta from rats fed a high-fat diet: role of aerobic exercise training.

The aim of the present study was to evaluate the effects of aerobic exercise training on perivascular adipose tissue (PVAT) function in thoracic aorta from rats fed a high-fat diet. Aortic vascular reactivity was performed in sedentary (SD), trained (TR), sedentary high-fat diet (SD-HF), and trained high-fat diet (TR-HF) male Wistar rats in the absence (PVAT-) or in the presence (PVAT+) of thoracic PVAT. We also measured circulatory concentrations of leptin and tumour necrosis factor alpha (TNF-α), as well as the protein expressions of TNF-α receptor 1 (TNFR1) and inducible nitric oxide synthase (iNOS) on PVAT. In the SD-HF group, the body weight, epididymal fat pad, thoracic PVAT, circulatory triglycerides, insulin, leptin and TNF-α were increased when compared with the SD group, whereas exercise training reduced these values in TR-HF group. The relaxing response curves to acetylcholine and sodium nitroprusside were not modified by either intervention (high-fat diet or exercise training) or the presence of PVAT. The presence of PVAT had an anti-contractile effect in response to serotonin in all groups. In SD-HF group, the increased magnitude of anti-contractile effects was in parallel with an up-regulation of iNOS protein expression in PVAT without alteration in TNFR1. Exercise training was effective in normalizing the vascular reactivity in rings PVAT+ and in reducing the iNOS protein expression. Exercise training prevented the PVAT-induced alteration in thoracic aorta from rats fed a high-fat diet.

Circulating Concentrations of Adipocytokines and Their Receptors in the Isolated Corpus Cavernosum and Femoral Artery from Trained Rats on a High-Fat Diet.

BACKGROUND: The aim of the present study was to evaluate different signaling pathways by which exercise training would interfere in endothelial function in obesity. Therefore, we examined adipocytokine levels and their receptors in the corpus cavernosum and femoral artery from trained rats on a high-fat diet. METHODS: Functional experiments were performed in control sedentary and trained rats, and sedentary (h-SD) and trained male Wistar rats on a high-fat diet (h-TR). Nitric oxide (NO) and reactive oxygen species (ROS) were evaluated in vascular tissue. Circulating adipocytokines and their receptors were analyzed. RESULTS: In the h-SD group, the maximal responses to acetylcholine (ACh) were reduced in the femoral artery and corpus cavernosum as well as the electrical field stimulation, accompanied by an increase in circulating insulin, leptin, TNF-α, MCP-1, and PAI-1. Downregulation of ObR protein expression in the femoral artery was observed without alterations in AdipoR1 and TNFR1 in both preparations. A positive effect was observed in the h-TR group regarding the relaxation response to ACh and circulating adipocytokines, resulting in increased NO production and reduced ROS generation. Exercise restored the ObR protein expression only in the femoral artery. CONCLUSION: Aerobic exercise training ameliorated the inflammatory adipocytokines and restored the relaxation responses in the corpus cavernosum and femoral artery in rats on a high-fat diet.