2571-P: An Olive-Derived Small Molecule Enhances Liraglutide-Induced Weight Loss in Diet-Induced Obesity

Introduction and Objective: Moderate to substantial weight loss is associated with reduced obesity-related metabolic risk and improved glycemic control in type 2 diabetes. Identifying strategies that enhance weight loss remains a critical need for metabolic disease management. We investigated whether liraglutide combined with elenolic acid (EA), a bioactive small molecule that improves weight and glycemic control, further enhances metabolic outcomes in diet-induced obese (DIO) mice. Methods: DIO male mice were treated for 44 days with EA (50 mg/kg), liraglutide (100 µg/kg), a combination of EA and liraglutide, or vehicle. Body weight and food intake were measured every 4 days. Glucose homeostasis and insulin sensitivity were assessed after 30 days of treatment using oral glucose tolerance tests (OGTT), intraperitoneal glucose tolerance tests (IPGTT), and insulin tolerance tests (ITT), with area under the curve (AUC) calculated. Results: After 44 days, combined EA and liraglutide treatment resulted in significantly greater weight loss (12.94 g; 24.72%) compared with EA (3.76 g; 7.23%) or liraglutide alone (6.40 g; 12.04%). This was accompanied by greater reductions in average daily and cumulative food intake (1.90 g/day and 81.13 g, respectively) compared with EA-treated (2.43 g/day and 103.03 g) and liraglutide-treated mice (2.30 g/day and 96.90 g). During OGTT, glucose responses in the combination group were significantly improved and comparable to EA alone, whereas during IPGTT, glucose AUC was reduced to levels similar to liraglutide. In ITT, combination treatment improved insulin sensitivity to a degree comparable to liraglutide. Conclusion: Co-administration of EA and liraglutide produced greater weight loss than either monotherapy alone and integrated complementary metabolic effects, supporting the potential of EA-based combination strategies for more effective obesity management. Disclosure H. Alkhalidy: None. X. Cao: None. R.S. Vaughan: None. M.T. Rachi: None. D. Liu: None. Funding National Institutes of Health (R01DK134401-01)