Investigation of effects of PPAR-γ agonist pioglitazone on perivascular adipose tissue

Perivascular adipose tissue (PVAT) plays a role in many physiological and pathological processes, such as regulation of vascular tone, vascular inflammation and atherosclerosis. The aim of our study is to evaluate the changes in the structure and function of PVAT in type 2 diabetes (T2DM) and to investigate the possible role of PPARγ agonist pioglitazone. In our study, it was aimed to examine the effect of pioglitazone treatment on PVAT dysfunction that occurs in a pathological condition such as T2DM. For this purpose, the effects of 20mg/kg oral pioglitazone administration for 6 weeks in HFD/STZ T2DM model in Wistar albino male rats on biochemical parameters (fasting glucose, OGTT, total cholesterol and triglyceride), amount of PVAT, vascular reactivity, adipokine (adiponectin and leptin) and inflammatory cytokine (TNF-α and IL-6) levels, various gene expression levels in PVAT were evaluated. In addition, heart, liver, thoracic aorta and PVAT samples were evaluated histopathologically. Our findings showed that pioglitazone administration showed positive effects on blood glucose and lipid profile in the HFD/STZ T2DM model in rats, increased the amount of PVAT, however, it did not significantly change the anticontractile effect of PVAT on vascular reactivity, and had no effect on endothelium-mediated or non-endothelium-mediated relaxation responses. Pioglitazone administration increased TNF-α levels while not changing adiponectin, leptin and IL-6 levels. It also significantly increased PPAR-γ expression levels in PVAT tissue in the diabetes group. In addition, pioglitazone caused a significant decrease in autophagy-related Beclin and LC3-II gene expression levels in the diabetes group. Histopathological findings support existing clinical studies. In addition, pioglitazone administration increased adipocyte size in PVAT. We think that our findings will add a different dimension to the understanding of the effects of pioglitazone on the cardiovascular system.