2090-P: Role of Thromboxane-Prostanoid Receptor in Obesity Related Insulin Resistance

Abstract

Background: Thromboxane-Prostanoid Receptor (TP-R) is implicated in several chronic inflammatory disorders. Our preclinical animal studies showed that TP-R plays a critical role in obesity linked Insulin Resistance (IR). Aim: To determine the link between TP-R and obesity and/or obesity-associated inflammation/IR in human subjects. Methods: We collected PBMCs from lean normal and obese IR subjects and analyzed the expression of various inflammatory genes including TP-R, Thromboxane A2 Synthase (TXA2S), TNFα, and MCP-1. We obtained subcutaneous adipose tissue biopsies from obese subjects and analyzed the TP-R mRNA expression and its correlation with inflammatory cytokines mediating IR. Results: TP-R mRNA expression is significantly increased in PBMCs of obese IR subjects compared to lean normal subjects (P<0.04 by Wilcoxon rank-sum test). In addition, PBMC TP-R expression is positively correlated with the expression of TXA2S, a gene involved in thromboxane A2 synthesis (n=29, Spearman’s r=0.36, P=0.05). Moreover, TP-R expression is positively correlated with body weight, BMI and fat mass (Figure). In AT, TP-R expression is positively correlated with IL-8 expression (n=31, r=0.49, P<0.005). Conclusion: Our data demonstrate that TP-R expression is positively correlated with markers of obesity and/or IR and support our hypothesis that TP-R can be used as a biomarker or a therapeutic target for obesity related IR. Disclosure T. Thangavelu: None. S. Viswanathan: None. C. Desouza: Consultant; Self; Novo Nordisk A/S, Sanofi US. Funding National Institute of General Medical Sciences; Great Plains Institutional Developmental Award for Clinical and Translational Research