Efeitos do exercício no controle das propriedades do tecido adiposo perivascular e da vasodilatação mediada pela insulina

Abstract

Obesity is an important risk factor for cardiovascular diseases. The adipose tissue contributes for cardiovascular pathophysiology and in this work the focus was on a particular adipose tissue, the perivascular adipose tissue (PVAT). PVAT resides alongside arteries and that present a vasoregulatory property. Physical activity is one of the mainstays for prevention of chronic diseases, reducing adipose tissue mass and inflammatory profile. The hypothesis of the current work is that exercise and myokines improves obese PVAT physiology and, therefore vascular responses to insulin. To answer this question, the work was divided into two parts. Part one explored the ability of exercise and the myokines, interleukin 6 (IL-6) and 15 (IL-15) in modifying the phenotype of PVAT and muscle perfusion. For that purpose, isolated gracilis arteriolar responses were evaluated on the pressure myograph, in presence or not of its own PVAT. Muscle perfusion during hyperinsulinemia was tested with the contrast enhanced ultrasonography. The second part tested whether exercise could protect the microvasculature after high fat feeding (HFD). For that purpose, two-weeks high fat diet fed mice were exercised and had their cremaster muscle microcirculation challenged afterwards. Exercise improved body composition, regardless the high fat chow feeding. It also protected muscular microvasculature from fat-induced impairments, nevertheless it did not enhance the positive interaction between PVAT and insulin-induced vasodilatation. IL-15 presented a contradictory dataset, at the same time that it blocked PVAT interaction with insulin-induced vasodilatation, once the alpha subunit of its receptor was deleted from the mice, no muscle perfusion was seen during hyperinsulinemia. In conclusion, exercise presented two antagonic effects: one directly in resistance arterioles and a second inhibitory one over PVAT, which was mimicked in presence of IL-15. Exercise per se did not improve insulin sensitivity, but it prevented microvascular impairments provoked by two weeks of high fat feeding. Although exercise did not increase muscle perfusion, the deletion of the alpha subunit from the IL-15 receptor suggests a role of L-15 in controlling normal perfusion. At last, exercise was able to protect the microcirculation from fat overload aggressions, when it modified PVAT and brown adipose tissue phenotypes.