Serum iron concentration and leptin inversely relate, partially mediated by body mass index in American adults

Iron metabolism and leptin are interconnected, and both link with obesity. In this cross-sectional study, we hypothesized that serum iron markers associate with leptin, with body mass index (BMI) acting as a mediator, confounder, and effect modifier in this relationship. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) III, with a focus on serum iron markers and leptin. The relationship between serum iron markers and leptin was determined by multiple linear regression. The Bootstrap method was employed to investigate the mediating effect of BMI on this association. Among 3888 American adults, serum iron (SI) and transferrin saturation (TS) showed a negative association with leptin (log2-transformed) (β: -0.010, 95% confidence interval [CI]: -0.013 to -0.006, P < 0.001; β: -0.006, 95% CI: -0.008 to -0.004, P < 0.001). Total iron binding capacity (TIBC) was positively associated with the serum concentration of leptin (log2-transformed) (β: 0.002, 95% CI: 0 to 0.004, P = 0.0292). Sex, BMI, and body fat percentage significantly influenced these associations. Notably, the association between the iron markers and leptin diminished in individuals with a BMI ≥ 30 kg/m 2. There was no observable relationship between leptin and serum ferritin (SF) concentrations. BMI mediated 4.81% of the SI-leptin association, with no mediation of body fat percentage. Our study identified a link between SI and leptin, with BMI as a mediating factor. In clinical settings, it is vital to understand how treatments targeting iron metabolism can directly impact serum leptin concentration and the subsequent physiological changes.