THU115 Sex-Specific And Shared Associations Between Vasopressin Levels And Body Composition In Adults With Obesity

Disclosure: F. Galbiati: None. M. Wronski: None. A. Aulinas Maso: None. M. Muhammed: None. R. Boutin: None. K. Liya: None. S. Carter: None. H. Nazarloo: None. J.M. Davis: None. K. Holman: None. J. Gydus: None. S. Smith: None. E. Asanza: None. M. Bredella: None. M. Torriani: None. F. Plessow: None. E.A. Lawson: Advisory Board Member; Self; OXT Therapeutics. Grant Recipient; Self; Tonix Pharmaceuticals. Background: Arginine-vasopressin (AVP) is a sexually dimorphic neurohormone shown in preclinical studies to have relevant metabolic effects, including reducing food intake, inducing lipolysis, and promoting muscle regeneration in male mice. However, findings are inconsistent, possibly due to the opposing effects of AVP at different receptor subtypes, and little is known about the effects of AVP on metabolism in humans. We hypothesized that AVP may act as signal of energy availability, such that in adults with obesity, integrated AVP levels around a standardized meal would be positively associated with BMI, adiposity, and lean mass. We also predicted that relationships between AVP and body composition measures would differ by sex. Methods: We performed a cross-sectional study of 53 adults with obesity (56% females; age [mean±SD] 33.7±6.2 years; BMI 36.9±4.9 kg/m(2)). We obtained plasma AVP levels fasting and 30, 60, and 120 minutes after a standardized meal. We computed area under the curve with respect to ground (AUC) for an integrated measure of AVP levels around the meal. Participants underwent body composition assessment by dual-energy X-ray absorptiometry (total fat, truncal fat, and lean mass) and magnetic resonance imaging (abdominal visceral and subcutaneous fat). We performed Pearson’s correlation (normally distributed variables) and Spearman’s correlation (non-normally distributed variables) to investigate the relationship between AVP levels and body composition parameters. Fisher’s Z test was performed to analyze the difference between correlation coefficients across sexes. Results: Age and AVP AUC did not differ based on sex (p=0.300). Total fat mass (p=0.013) was higher while total lean mass (p<0.0001) and abdominal visceral fat (p=0.001) were lower in females than males; BMI, truncal fat, and abdominal subcutaneous fat did not differ by sex (p’s≥0.09). Across all participants, AVP AUC levels were positively correlated with BMI (rs=0.36, p=0.008), total fat mass (r=0.33, p=0.013), truncal fat (r=0.35; p=0.010), abdominal subcutaneous fat (r=0.30, p=0.028), and total lean mass (r=0.38, p=0.005), but not with abdominal visceral fat (p=0.331). Within sex-based group, a robust positive correlation between AVP AUC and abdominal subcutaneous fat mass was present in males (r=0.56, p=0.004), but not females (r=0.04, p=0.592) [(by Fisher’s Z test, p=0.024). There were no other sex differences in correlations (by Fisher’s Z test, p≥0.108). Conclusions: Our data in humans showing a link between integrated AVP and body composition support preclinical data indicating that AVP is a metabolically active hormone. Additionally, we identified sex differences in the relationship between AVP and subcutaneous fat mass. Further investigation of sex-specific and shared metabolic effects of AVP in humans will be important. Presentation: Thursday, June 15, 2023