SAT-059 Randomized Controlled Trial Examining Effects of 8 weeks of Intranasal Oxytocin on the Circulating Inflammatory Proteome in Adults with Obesity

Abstract Disclosure: R. Boutin: None. A.P. López: None. L. Dysart: None. F. Plessow: None. J. Lo: None. M. Misra: None. M. Bredella: None. K. Eddy: None. J. Thomas: None. M. Kingsbury: None. L.M. Holsen: None. S.E. Smith: None. E. Asanza: None. K. Holman: None. E.A. Lawson: Tonix, Merck, Up To Date, Thermo Fischer, Danahar Corporation, Zoetis, Intuitive Surgical, West Pharmaceutical. L. Breithaupt: None. Objectives: Excess adiposity is associated with low-grade inflammation that drives caloric intake, obesity, and comorbidities (e.g., cardiovascular disease, cancer). There are no FDA-approved treatments targeting inflammation to mitigate obesity-related comorbidities. Preclinical studies indicate that oxytocin (OXT), a hormone involved in energy balance and under investigation as an anti-obesity therapeutic, has anti-inflammatory properties. Single dose intranasal (IN) OXT modulates circulating inflammatory proteins in men, but the effects of prolonged OXT administration on inflammation in obesity remain unknown. We hypothesized that OXT would shift protein expression toward an anti-inflammatory profile. Methods: 61 adults with obesity (45% female; mean age 34 yrs, BMI 37) were randomized (1:1) to 8 weeks of intranasal (IN) oxytocin (OXT; n=31) or placebo (n=30). Serum samples were collected at baseline (BL), and weeks 4 and 8 for targeted analysis of the inflammatory proteome. Principal component analysis was used to visualize combined proteomic variance, and Q-Q plots were used to assess normality. To assess treatment effects, we used: (1) Analysis of Covariance to examine post-treatment (Weeks 4, 8) protein levels as a function of BL protein levels and treatment group, adjusting for BL differences and between group effects. (2) Within-group paired t-tests to assess change in protein levels from BL to post-treatment (Weeks 4, 8) within each treatment group. Mean differences were calculated, and p-values were corrected for multiple comparisons using the Benjamin-Hochberg (BH) method. Results: BL protein levels predicted week 4 protein expression for all tested inflammatory markers (e.g., EN-RAGE: β = 0.30, p = 0.002; FGF-23: β = 0.24, p = 0.044). Treatment group effects were observed for several proteins (e.g., EN-RAGE: β = 0.30, uncorrected p = 0.002, BH-corrected p = 0.145). Within-group analyses demonstrated significant changes in several proteins from BL to week 4 in the IN OXT group, including increases in EN-RAGE (mean difference = 0.17, uncorrected p = 0.030), IFN-γ (mean difference = 0.40, uncorrected p = 0.041), and FGF-23 (mean difference = 0.16, uncorrected p = 0.010). For the placebo group, pro-inflammatory protein levels generally decreased over time. Although treatment- and within-group changes did not remain significant after BH correction, these findings suggest a possible trend toward differential protein modulation by IN OXT. Discussion: OXT increased proinflammatory proteins that promote gut and blood brain barrier (BBB) permeability. The increase in EN-RAGE, which binds and transports OXT across gut and BBB, is consistent with previously reported effects of single dose IN OXT in modulating the RAGE pathway. Loss of significance after BH correction is likely due to limited statistical power. Further investigation is warranted. Presentation: Saturday, July 12, 2025