Exercise training prevents the perivascular adipose tissue-induced aortic dysfunction with metabolic syndrome

Abstract

The aim of the study was to determine the effects of exercise training on improving the thoracic perivascular adipose tissue (tPVAT) phenotype (inflammation, oxidative stress, and proteasome function) in metabolic syndrome and its subsequent actions on aortic function. Methods: Lean and obese (model of metabolic syndrome) Zucker rats (n=8/group) underwent 8-weeks of control conditions or treadmill exercise (70% of max speed, 1 h/day, 5 days/week). At the end of the intervention, the tPVAT was removed and conditioned media was made. The cleaned aorta was attached to a force transducer to assess endothelium-dependent and independent dilation in the presence or absence of tPVAT-conditioned media. tPVAT gene expression, inflammatory /oxidative phenotype, and proteasome function were assessed. Results: The main findings were that Ex induced: (1) a beige-like, anti-inflammatory tPVAT phenotype; (2) a greater abundance of •NO in tPVAT; (3) a reduction in tPVAT oxidant production; and (4) an improved tPVAT proteasome function. Regarding aortic function, endothelium-dependent dilation was greater in exercised lean and obese groups vs. controls (p < 0.05). Lean control tPVAT improved aortic relaxation, whereas obese control tPVAT decreased aortic relaxation. In contrast, the obese Ex-tPVAT increased aortic dilation, whereas the lean Ex-tPVAT did not affect aortic dilation. Conclusion: Overall, exercise had the most dramatic impact on the obese tPVAT reflecting a change towards an environment with less oxidant load, less inflammation and improved proteasome function. Such beneficial changes to the tPVAT micro-environment with exercise likely played a significant role in mediating the improvement in aortic function in metabolic syndrome following 8 weeks of exercise. Keywords: Perivascular adipose tissue, Metabolic syndrome, Proteasome, Oxidative stress, Exercise