369 Investigating the impact of bariatric surgery on metabolic mechanisms that promote obesity-associated inflammation in subjects with and without Type 2 Diabetes

OBJECTIVES/GOALS: This project will provide novel insights into mechanism(s) by which differences in inflammation develop & resolve, or fail to resolve, in metabolically different groups of bariatric surgery patients determined by Type 2 Diabetes status. My work may uncover unique differences between cohorts, encouraging development of personalized medicine. METHODS/STUDY POPULATION: I analyzed human blood samples collected before and 3, 6, & 12 months after bariatric surgery at the University of Kentucky through an established tissue bank. Subjects hadnormal glucose tolerance, pre-diabetes, or Type 2 Diabetes, based on HbA1c%. Iisolated peripheral blood mono nuclear cells & will comparecytokine profiles among cohorts across all time points. I will define & perturbmetabolic differencesin immune cells among cohorts & across time via isotope tracing, fuel source limitation, and metabolite inhibition. This will determine causal relationships between cytokine profiles & immune cell metabolism. RESULTS/ANTICIPATED RESULTS: I anticipatecytokine profiles, a functional output of immune cells, will differ among cohorts pre-surgery, and that this difference will diminish post-surgery. Differencesmay be insignificant by the 12 month time point. I also anticipate differences in fuel usage and metabolite productionin immune cells among cohorts pre-surgery, and that these differences only partially resolve post-surgery to poise immune cells for continued chronic inflammatory action. I hypothesize that T2D status has a lasting impact on immune cell function and fuel usage patterns, and will continue to supportchronic inflammation following short term T2D remission and longer-term weight loss. DISCUSSION/SIGNIFICANCE: There has been an alarming increase in obesity and its comorbidities over recent decades, and inflammation is a known supporter of T2D. The anticipated rewiring of immune cell metabolism post-surgery, if incomplete, may poise subjects forweight regain and T2D recurrence.