Identification of intranasal oxytocin plasma proteome signatures.
BACKGROUND: The hypothalamic peptide oxytocin regulates a range of central and peripheral activities, ranging from uterine contractions to energy homeostasis. Oxytocin-based therapeutics are under investigation for neuropsychiatric and metabolic disease, including obesity. The mechanisms underlying oxytocin effects are poorly understood. This study profiles 4725 serum proteins in 19 healthy men across the adiposity spectrum (9 normal-weight, BMI < 25 kg/m2; 10 overweight/obese, BMI ≥ kg/m2) following exogenous, intranasal oxytocin administration to identify markers of pharmacodynamic effect. METHODS: In a double-blind, randomized controlled crossover design, 25 men were exposed to a single dose of 24 IU intranasal oxytocin vs. placebo. Fasting blood was drawn immediately prior and at 15, 30, and 55 min after oxytocin/placebo administration for proteomic analysis (SOMA Scan, Soma Logic, Inc.). RESULTS: As previously reported in the parent study, intranasal oxytocin reduced caloric intake at the test meal; here, we examined proteomic predictors of this behavioral effect. Proteomic data was available for 19 men. We identified 198 differentially expressed proteins in response to intranasal oxytocin in fasting men across the adiposity spectrum. The pathways identified are involved in intracellular signaling pathways, as well as immune regulation and inflammation. Oxytocin modulated a cluster of proteins that was associated with subsequent caloric intake at the test meal. CONCLUSIONS: These data provide insights into mechanisms underlying pharmacologic oxytocin effects on human physiology and a framework for future investigations.