SUN-637 Changes in insulin sensitivity and circulating adipokines following estrogen deprivation in mice

Abstract Disclosure: A. LaMothe: None. L. Marino: None. F.S. Celi: None. S. Doan: None. Background: Menopause is associated with weight gain and increased risk for obesity-related metabolic dysfunction including type 2 diabetes, hypertension, and increased risk for cardiovascular disease. Estrogen signaling plays an important role in modulating adipocyte biology, but the interplay between estrogen, adipokines, and carbohydrate metabolism remains unclear.1 To explore this interaction, we examined the effects of acute estrogen deprivation on adipokines levels and carbohydrate metabolism. Objective: To assess changes in carbohydrate metabolism and circulation, perform an observational study of leptin and adiponectin transcription in adipose tissue. We aim to investigate this relationship via murine models of adipose tissue-specific loss of estrogen signaling (either alpha or beta). Methodology: Six 8-weeks old C57B6J mice underwent fasting tail vein blood sampling for leptin, adiponectin, fasting glucose and insulin. Ovariectomy as then performed. Serum Adiponectin, Leptin, and Insulin were measured by ELISA, glucose by Accu-check. Statistical analysis was performed by unpaired t-test, nonparametric data were analyzed using Mann-Whitney test. Results: Compared to baseline, post-ovariectomy serum glucose and insulin were 169.6 ± 23.2 vs. 191.5 ± 14.0, ng/mL p= 0.56 and 1.76 ± 0.33 vs. 2.53 ± 0.38 mg/dl p = .19, respectively. Post ovariectomy, HOMA-IR was significantly reduced 19.80 ± 2.78 vs. 33.41 ± 3.6 p = 0.03. Conversely, compared to baseline, adiponectin and leptin levels were significantly increased 12144 ± 576 vs. 9251 ± 554 ng/mL, p= 0.014 and 8.523 ± 0.8497 vs. 3.607 ± 0.5184 ng/mL, p= 0.0012 respectively. Conclusions: Our results indicate an increase in insulin sensitivity following acute estrogen deprivation, accompanied by significant increase in adiponectin and leptin. The increased adiponectin concentration, but decreased adiponectin:leptin ratio suggests the changes in insulin sensitivity in this model of estrogen deprivation are driven by changes in adipokines.2 A limitation of this study is the single time point, and we cannot rule out that the changes observed may be driven by changes in food intake secondary to surgical trauma. Additional studies with multiple time points and dietary manipulations will be necessary to better understand the role of estrogen deprivation on adipose tissue metabolism, adipokine secretion, and insulin sensitivity. References: 1. Tamakoshi, Koji et al. “The transition to menopause reinforces adiponectin production and its contribution to improvement of insulin-resistant state.” Clinical endocrinology vol. 66,1 (2007): 65-71. 2. Yoon, Myeong Jin et al. “Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor alpha.” Diabetes vol. 55,9. Presentation: Sunday, July 13, 2025