Abstract 115: Downregulation of Perivascular Adipose Tissue PPAR Gamma in Western Diet-Induced Persistent Vascular Dysfunction in Female Rats

Abstract

Consumption of a western diet (WD) is a major part of modern life contributing to the epidemic of Metabolic Syndrome (MS), a significant risk factor for cardiovascular disease. Recent studies from our laboratory have characterized a model of WD induced MS in female rats. Adopting a healthier diet may be sufficient to reverse the constellation of metabolic symptoms associated with MS including obesity-related hypertension. However, it remains unclear if returning to a normal diet overcomes cardiovascular dysfunction associated with MS. We hypothesized that cardiovascular dysfunction will persist despite diet reversal due to altered PPAR-γ, an important vascular tone regulator, in the perivascular adipose tissue (PVAT). Eight-week old female Wistar rats were fed a WD (21% fat, 50% carbohydrate (34% sucrose) for 20 weeks (WD group) to induce MS. Then, the rats were subjected to diet reversal for 8 weeks (rWD group). The control group received a regular chow diet (5% fat, 48.7% carbohydrate (3.2% sucrose). WD group exhibited increased body weight, triglyceride levels, intolerance to glucose and systolic blood pressure characterizing MS. Direct measurement of blood pressure via right carotid catheterization showed that WD increased systolic blood pressure (141.61 ± 10 vs. 119.52 ± 9 mmHg) compared with controls. Strikingly, diet reversal was unable to drop systolic blood pressure (139.87 ± 13 mmHg). WD impaired acetylcholine and sodium nitroprusside-mediated relaxation in aortic rings. These effects remained unchanged even after diet reversal. Expression of PPAR-γ in aortic PVAT was significantly reduced in the WD group (3.2 fold) and in the rWD group (2.4 fold ) compared with controls. Moreover, we found high levels of lysine acetylation in the PVAT from WD (2.8 fold ) and rWD group (2.0 fold) compared with controls. Despite reversal WD led to significant improvement of all metabolic parameters, including weight loss, this strategy was unable to reverse vascular dysfunction and elevated blood pressure caused by WD consumption. Decreased PPAR-γ expression in PVAT associated with hyperacetylation will be further examined as a potential mechanism underlying persistent vascular dysfunction in WD-induced MS.