Oxytocin, disordered eating, and insulin resistance: a mediation analysis in adults with metabolic dysfunction

Aim: Dysregulated eating behavior is closely linked to metabolic dysfunction and may represent a behavioral pathway connecting neuroendocrine signaling to insulin resistance. Oxytocin has emerged as a potential regulator of feeding behavior and food-related reward processing, but the mechanisms linking endogenous oxytocin to metabolic health remain unclear. This study examined whether eating psychopathology mediates the association between circulating oxytocin concentrations and insulin resistance. Methods: In this cross-sectional study, 99 adults with varying metabolic obesity phenotypes completed validated assessments of eating behavior, including emotional eating, external eating, and global eating psychopathology (Eating Disorder Examination Questionnaire, EDE-Q). Plasma oxytocin concentrations and metabolic parameters were measured under standardized conditions. Associations were evaluated using correlation and regression-based mediation analyses with bootstrap estimation (5,000 resamples), adjusted for age and body mass index. Results: Lower oxytocin concentrations were significantly associated with higher eating psychopathology, particularly emotional and external eating. Eating psychopathology was positively associated with insulin resistance (HOMA-IR). Mediation analysis demonstrated a significant indirect association between oxytocin and HOMA-IR through eating psychopathology (ab = −0.181; 95% CI [−0.353, −0.064]), whereas the direct effect was not significant. Similar patterns were observed for emotional and external eating. Because analyses were cross-sectional, the identified mediation pathway represents a statistical indirect association rather than evidence of causality. Conclusions: Lower endogenous oxytocin concentrations were associated with greater eating psychopathology and higher insulin resistance. These findings suggest that behavioral pathways may contribute to the observed association between oxytocin and metabolic dysfunction. However, the cross-sectional design precludes causal inference, and the observed mediation should be interpreted as a statistical association rather than a mechanistically established pathway.