Mediating effect of serum lipids on the BMI–uric acid association: A cross-sectional study

Uric acid (UA) acts as an antioxidant but, when elevated, contributes to gout. Higher body mass index (BMI) is consistently linked to increased UA, and dyslipidemia correlates with UA levels. However, the extent to which these lipid fractions mediate the BMI-UA relationship remains limited, especially in the context of aging populations in China. This study aims to investigate the association between BMI and UA among Chinese adults and to quantify the mediating roles of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) in this relationship using nationally representative China Health and Retirement Longitudinal Study (CHARLS) data. We analyzed cross-sectional data from 8238 participants in the 2011 wave of the CHARLS, serum lipids were measured via standard CHARLS protocols. Covariates included demographics, lifestyle, clinical history, blood pressure, fasting glucose, sleep, and physical activity. Two multivariable linear regression models estimated the BMI-UA association before and after adjusting for TG, TC, HDLC, and LDLC. A parallel mediation analysis decomposed BMI's total effect on UA into direct and indirect components via each lipid parameter, using 5000 bootstrapped samples. Multivariable linear regression showed that BMI was positively associated with UA (β = 0.12, P < .001, adjusted R2 = 0.19). After adjusting for lipid mediators, the association remained significant but attenuated (β = 0.09, P < .001, adjusted R2 = 0.23). Mediation analysis revealed that high serum TG, TC, and HDLC explain a meaningful part (28.4%) of the BMI-UA association (total indirect effect = 0.714, 95% confidence interval: 0.557-0.881), whereas LDLC shows no significant mediating role (indirect effect = -0.118, 95% confidence interval:-0.267-0.021). Serum TG, TC, and HDLC explain a meaningful part of the BMI-UA association, whereas LDLC shows no significant mediating role. These results highlight lipid metabolism as one pathway linking adiposity with urate levels and warrant confirmation in larger cohorts and mechanistic investigations.