2570-P: Elenolic Acid Improves Metabolic Control and Potentiates Metformin Efficacy in a Preclinical Model of Postmenopausal Obesity and Diabetes

Introduction and Objective: Estrogen deficiency in postmenopausal women promotes increased appetite, weight gain, and metabolic dysfunction. Ovariectomized (OVX) mice fed a high-fat diet (HFD) serve as a well-established model of postmenopausal metabolic impairment. Elenolic acid (EA), an olive-derived bioactive compound, has demonstrated metabolic benefits in male models; however, its effects under estrogen-deficient conditions remain unclear. Therefore, this study aimed to determine the metabolic effects of EA in a mouse model of postmenopausal metabolic dysfunction. Methods: Female mice underwent sham surgery or ovariectomy and were fed chow diet or HFD for 10 weeks, followed by daily oral gavage with vehicle, EA (50 mg/kg), metformin (300 mg/kg), or EA plus metformin for 40 days. Body weight (BW) and food intake (FI) were monitored, acute feeding was assessed by 24-hour intake tests, and glucose homeostasis was assessed by blood glucose measurements and glucose and insulin tolerance tests. Results: HFD-fed OVX mice exhibited increased FI, greater BW gain, and impaired glucose homeostasis compared with sham controls. EA significantly reduced FI, attenuated BW gain, and improved glucose tolerance and insulin sensitivity in OVX mice. Chronic EA treatment also reduced the early postprandial feeding response during acute feeding tests. Metformin alone produced modest metabolic benefits compared with EA, while combined EA and metformin treatment synergistically reduced FI, BW gain, and glucose homeostasis in OVX mice. Conclusion: EA improves feeding behavior, BW regulation, and glucose homeostasis in OVX mice fed an HFD, supporting its potential as an adjunct strategy for postmenopausal obesity and type 2 diabetes. Disclosure R.S. Vaughan: None. X. Cao: None. H. Alkhalidy: None. M.T. Rachi: None. D. Liu: None. Funding National Institutes of Health (R01DK134401-01)