Associations of Metal Mixtures with Lipid Profiles: Exploring the Mediating Role of Testosterone in a Cross-Sectional...

Metal exposure is a critical driver for dyslipidemia, yet the associations and underlying mechanisms between them remain uncertain. This study aimed to investigate the relationships between metal exposure, lipid profile, and total testosterone (TT) and to explore the mediating role of TT in 548 manganese-exposed male workers. We quantified 15 blood metals alongside serum lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)] and TT levels. Least absolute shrinkage and selection operator (LASSO) was used to select key metals. Bayesian kernel machine regression (BKMR) and generalized linear regression (GLM) were performed to explore the associations among key metals, lipid profiles and TT. Mediation analysis was used to evaluate mediating role of TT between metal and lipid profile. BKMR indicated that Pb-dominated (PIP = 0.72) mixtures (Pb, Cu, As, Se) elevated HDL-C, whereas Cu-dominated (PIP = 0.42) mixtures (Mg, Cu, As, Se) reduced TT. GLM revealed that Pb (β = 0.05) and Se (β = 0.18) were positively associated with HDL-C, whereas Cu was inversely correlated with TC (β =  - 0.16), HDL-C (β =  - 0.20) and LDL-C (β =  - 0.34). Mg (β =  - 0.31) and As (β = 0.09) were significantly associated with TT. Mediation analysis revealed that TT mediated 8% (P < 0.05) effect between Cu and LDL-C. In conclusion, exposure to metal was associated with lipid profile in male occupational population. TT may play a potential mediating role between Cu and LDL-C, emphasizing the potential mechanism of endocrine system in metal-induced lipid abnormalities.