Abstract P302: A Positive Correlation Between High Levels of Inflammatory Markers and Angiotensin II in Obese Appalachian Females

Abstract

Introduction/Background: Obesity increases levels of certain biomarkers related to metabolic syndrome (leptin and TNF-α) in Appalachian women. It also leads to vascular dysfunction and atherosclerosis, which is assessed by levels of inflammatory markers angiotensin II (Ang II), a powerful vasoconstrictor, and serum adiponectin. We previously demonstrated a marked increase in levels of inflammatory markers in humans and mice with hypertension, obesity, and diabetes, and hypothesize that a high-BMI subject would present with increased levels of angiotensin II, leptin, and TNF-α, as well as decreased adiponectin. Methods: Serum adiponectin, Ang II, leptin, and TNF-α were assayed in female Appalachian subjects. Linear regression analysis was used to analyze the relationship between BMI, leptin, adiponectin, and Ang II. Nonlinear regression was used to determine the odds ratio and confidence intervals. The effect on murine pre-adipocytes was also measured. Results: Lipidomic analysis revealed a significant increase in Ang II among high-BMI females (50-72) compared to lower-BMI subjects (32-45) (p<0.05). Treatment of murine pre-adipocytes with Ang II decreased serum adiponectin levels and increased adipogenesis by 70% (p<0.05), implicating both Ang II and oxidative stress as factors in the pathogenesis of BMI-related disease. Serum leptin and TNF-α were significantly increased in high-BMI subjects (p<0.05) compared to lower-BMI subjects, while adiponectin levels were decreased (p<0.05) in high-BMI subjects compared to lower-BMI subjects. Discussion/Conclusions: Increased BMI in Appalachian females correlates with an increase in Ang II level, serum TNF-α, and leptin expression, and a decrease in serum adiponectin. This represents a novel mechanism by which high-BMI females with controlled blood pressure remain sensitive to the development of atherogenesis, vascular dysfunction, and metabolic syndrome.