Abstract P034: Increased Toll-Like Receptor 4 In Perirenal Adipose Tissue Is Associated With Elevated Systolic Blood Pressure In Obese Mice

Abstract

Obesity is a major risk factor for the development of vascular dysfunction and hypertension. According to the Framingham Heart Study, obesity accounts for 70% of cases of primary hypertension. Emerging evidence suggests that perirenal adipose tissue (PRAT) is linked to cardiovascular complications in obesity. Whether PRAT is linked with blood pressure regulation in obesity remains unknown. We hypothesize that, in obesity, PRAT expands and activates local Toll-like receptor 4 (TLR4), a key factor of the immune system, in association with increased systolic blood pressure (SBP). Eight-week-old male and female C57BL6 mice were randomized into two experimental groups. The control group (n=10) received a standard chow diet (5% fat, 48.7% carbohydrates [3.2% sucrose]) and the obese group (n=10) received a Western Diet (WD) (40% fat, 43% carbohydrates [34% sucrose]) for 38 weeks. Central obesity was confirmed by increased body weight (Females: 34.88 ± 2.71 g vs. 22.86 ± 0.68 g controls, p<0.001; Males: 45.39 ± 1.98 g vs. 29.21 ± 0.79 g controls, p<0.0001), BMI (Females: 0.37 ± 0.01 kg/m2 vs. 0.27 ± 0.01 kg/m2 controls, p<0.0001; Males: 0.45 ± 0.02 kg/m2 vs. 0.32 ± 0.01 kg/m2 controls, p<0.001), and waist circumference (Females: 8.95 ± 0.44 cm vs. 7.65 ± 0.17 cm controls, p<0.05; Males: 10.79 ± 0.25 cm vs. 8.70 ± 0.16 cm controls, p<0.0001). Significant increase in PRAT weight was detected in the WD groups (Females: 11.78 ± 1.79 mg/g vs. 3.19 ± 0.31 mg/g controls, p<0.05; Males: 17.42 ± 2.34 mg/g vs. 2.92 ± 0.43 mg/g controls, p<0.001). By using radiotelemetry system, we found that SBP was significantly increased in the WD male group in the light cycle (125.12 ± 2.11 mmHg vs. 115.19 ± 2.19 mmHg controls, p<0.05) and dark cycle (132.42 ± 1.72 mmHg vs. 123.13 ± 1.67 mmHg controls, p<0.05). Strikingly, TLR4 expression in PRAT from male obese mice was significantly increased (2.1 fold of increase, p<0.05). In conclusion, our results show that obese male mice exhibit expanded PRAT with increased TLR4 expression in association with elevated SBP, suggesting a local inflammation in PRAT potentially contributing to disturbance of renal mechanisms of blood pressure regulation.