The association between obesity and telomere shortening is mediated through total bilirubin.

<h4>Background</h4>Both obesity and oxidative stress are closely linked to leukocyte telomere(definition) length (LTL) shortening, yet the specific mediating role of total bilirubin in this association remains insufficiently explored. This study aimed to quantify the extent to which total bilirubin, a potent endogenous antioxidant, mediates the association between obesity and LTL.<h4>Methods</h4>We analyzed data from 6,717 adults participating in the National Health and Nutrition Examination Survey 1999-2002. Causal mediation analysis with 1,000 bootstrap iterations was employed to investigate the mediating effect of serum total bilirubin on the association between body mass index (BMI) and LTL.<h4>Results</h4>In the fully adjusted model, BMI was significantly and inversely associated with LTL, with a total effect of -3.532 base pairs (bp) per 1-unit increase in BMI (95% confidence interval [CI]: -6.225 to -1.178; P = 0.002). Serum total bilirubin significantly mediated this association (average causal mediation effect = -0.446 bp; 95% CI: -0.726 to -0.237; P < 0.001). The estimated proportion of the association explained by bilirubin was 13.2% (95% CI: 5.5% to 41.2%; P = 0.002). A series of sensitivity analyses confirmed the robustness and stability of these mediation findings.<h4>Conclusions</h4>Total bilirubin serves as a significant statistical mediator in the relationship between obesity and LTL shortening. However, given the cross-sectional design of this study, further longitudinal investigations are required to confirm these associations and establish causality.