MON-LB021 Effects of Intranasal Oxytocin on the Fasting Serum Proteome in Healthy Lean and Obese Men

Background: The neuropeptide oxytocin (OT) may have metabolic effects, including regulation of energy intake, fat oxidation, and insulin sensitivity. However, the mechanisms underlying the metabolic effects of OT are not well understood. Objective: To examine proteome-wide alterations in response to intranasal OT in serum of healthy lean and obese men. Methods: 25 healthy men, [13 lean (mean±SD body mass index (BMI) 21.2±1.4 kg/m(2)) and 12 obese (BMI 31.5±4.8 kg/m(2))] mean age 27.1±7.8 years, completed a randomized, placebo-controlled crossover study of a single-dose of 24 IU intranasal OT (1). Fasting blood was drawn immediately prior (T0) and at 15, 30, and 55 minutes after OT/placebo administration for proteomic analysis (SOMAScan, SomaLogic, Inc.). The number of proteins and pathways that significantly changed from T0 to the mean post-dose, fasting measurement (T15-T55) in OT vs. placebo was determined. Normalized protein levels were compared between treatment and adiposity groups using rank product testing. Overrepresentation of known pathways containing proteins with significantly different concentrations was evaluated by hypergeometric test. P-values were adjusted by the Benjamini-Hockberg method to determine false discovery rates (FDR). Significance at FDR of 5%. Results: A total of 4,785 proteins were identified in serum of lean and obese men. In response to OT, a total of 710 pathways were altered. In both lean and obese men, OT-responsive biological pathways included regulation of inflammatory pathways via IL4, IL5, IL6, and IL7 (e.g., STAT1 and NFkB), insulin signaling (e.g., G-protein coupled receptor 2 and AKT), leptin signaling (e.g., STAT1, STAT3, and JAK2); and regulation of lipid metabolic processes (e.g., phospholipase and protein kinase C). In obese men, OT-responsive pathways included regulation of white adipocyte differentiation (e.g., cyclin dependent kinase) and IL3 signaling (e.g., tyrosine and serine/threonine kinase). In lean men, OT-responsive pathways included regulation of the acute inflammatory response (e.g., C-reactive protein and IL6 signal transducer) and lipid localization (e.g., apolipoproteins B, F, and L1). Conclusions: Our results suggest that OT modulates metabolic and inflammatory processes in men, and the specific effects may vary by adiposity status. Further research is required to confirm these exploratory findings. A clearer understanding of the effects of OT on the serum proteome will improve the translational capacity of OT-based therapeutics for use in obesity and other metabolic diseases. References: 1. Lawson EA, et al. Oxytocin reduces caloric intake in men. Obesity. 2015;23:950-6. Sources of Research Support: NIH K23 MH092560 (EAL), R01 DK109932 (EAL), 1UL1 TR001102-01, P30 DK040561, 2P30DK046200, 1F32MH118824-01 (SGH); MGH Claflin Distinguished Scholar Award (EAL); Fundacion Alfonso Martin Escudero Grant (AA). Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.