1730-P: Thromboxane Signaling and Obesity-Related Insulin Resistance

Abstract

Background: Thromboxane A2 (TxA2), a lipid mediator plays a critical role in cardiovascular disease and chronic inflammatory disorders. TxA2 signaling is regulated by TxA2 synthase (Tbxas1), an enzyme that produces TxA2, and TxA2 receptor (Tbxa2r). Objective: To determine if Tbxa2r gene expression in adipose tissue (AT) is higher in obese insulin resistant (IR) subjects compared to overweight non-IR subjects. Methods: Insulin resistance was measured via a homeostatic model assessment of insulin resistance (HOMA-IR). Subcutaneous AT biopsies were obtained from overweight (BMI between ≥25 to <30) no IR and obese (BMI ≥30) IR (HOMA-IR>2.5) subjects. Gene expression of Tbxa2r and Tbxas1 were analyzed in tissue samples and compared between groups. Results: The mRNA levels of Tbxa2r and Tbxas1 were significantly higher in obese IR subjects compared to overweight subjects (P<0.05). A positive correlation was observed between AT expression of Tbxa2r and Tbxas1 (Spearman’s r=0.49, n=35, P<0.01). We noted a weak positive correlation between AT Tbxa2r and HOMA-IR (Spearman’s r=0.31, n=35, P<0.07). A positive correlation was also noted between AT Tbxas1 and HOMA-IR (Spearman’s r=0.42, n=37, P<0.05). Conclusion: Our data suggest that TxA2 signaling is activated in AT in obesity and is associated with the development of insulin resistance in obesity. Tbxas1 and/or Tbxa2r may be a potential therapeutic target for obesity-linked metabolic diseases. Disclosure D. Alcaraz Alvarez: None. S. Viswanathan: None. T. Thangavelu: None. N. Kumar: None. K. Kelley: None. C. Desouza: Consultant; Self; AstraZeneca, Bayer AG, Novo Nordisk A/S.