Arginine-Vasopressin Dynamics in Relation to Food Intake and 8-Week Intranasal Oxytocin Treatment in Adults With...

Oxytocin (OXT) and arginine-vasopressin (AVP) are structurally similar hypothalamic-pituitary peptides with broad physiologic actions including regulation of caloric intake and metabolism. While OXT is under investigation as an antiobesity therapeutic, there are no data on endogenous AVP levels in relation to eating behavior in humans. Further, the effects of exogenous OXT on AVP dynamics, which could affect safety of treatment given AVP effects on water balance, are not well understood.

This work aimed to define secretory dynamics of circulating AVP around a standardized meal and in response to 8 weeks (W) intranasal (IN) OXT vs placebo in adults with obesity.

Cross-sectional and longitudinal data were used from an 8-W randomized clinical trial at a tertiary academic center. Participants included 63 adults with obesity (56% women, age 33.7 ± 6.3 years) of whom 61 were randomly assigned 1:1 to 8-W IN OXT (24 IU) 4 times daily or placebo. Intervention included a standardized meal, IN OXT vs placebo. Main outcome measure was AVP levels before and 30, 60, and 120 minutes after a standardized meal at baseline, and W4, 6, and 8 after starting OXT or placebo.

In response to food intake, AVP levels decreased at 60 minutes (adjusted mean ± SE = 68.55 ± 9.64 pg/mL) compared to fasting (80.99 ± 11.22 pg/mL; P = .022). AVP levels did not significantly change over the course of 8-W IN OXT treatment vs placebo (P ≥ .544). There was no effect of body mass index (P ≥ .615) or sex (P ≥ .498) on AVP levels.

AVP levels decreased after food intake in adults with obesity, indicating a potential disruption in AVP signaling and possibly underlying obesity pathophysiology. Chronic IN OXT administration did not alter AVP levels, supporting safety of OXT-based therapeutics.