Association of Mixed Metal Exposure with Metabolically Healthy Obesity: Mediating Effects of Inflammatory Biomarkers
Abstract
Obesity represents a significant global public health challenge, typically characterized by metabolic disturbances such as elevated blood pressure and dyslipidemia. However, a subset of obese individuals exhibits no apparent metabolic abnormalities, a condition termed metabolically healthy obesity (MHO). As a distinct obesity phenotype, MHO has garnered increasing attention due to its potential progression to metabolically unhealthy obesity (MUO) in the absence of early intervention, which may lead to more severe health consequences. Nevertheless, the association between mixed metal exposure and MHO remains poorly understood, and further research is urgently needed to elucidate the impact of mixed metal exposure on MHO risk and its underlying mechanisms.
Objective
(1) To investigate the association between mixed metal exposure and MHO.
(2) To explore the mediating role of inflammatory biomarkers in the relationship between metal exposure and MHO.
Methods
The study included 1,380 participants, comprising 906 with metabolically healthy normal weight (MHNW) and 474 with MHO. The concentrations of 13 metals in morning urine samples were measured using inductively coupled plasma mass spectrometry (ICP-MS). Restricted Cubic Spline (RCS), Logistic regression, and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess the association between urinary metal concentrations and MHO. Quantile G-Computation (qgcomp) and Bayesian Kernel Machine Regression (BKMR) were utilized to evaluate the association between mixed urinary metal exposure and MHO. The "mediation" package in R software was used to explore the potential mediating effects of inflammatory biomarkers.
Results
Logistic regression results indicated that the concentrations of Cu, Zn, As, Mo, Cd, and Tl were significantly associated with MHO risk (P < 0.05). Among these, Zn and Mo showed consistent and significant associations with MHO across all models. LASSO regression identified Zn and Mo as key metals associated with MHO. The qgcomp results showed that, after adjusting for confounders, Mo, Cd, and As exhibited negative effects, while Zn, Cu, and Tl exhibited positive effects. Zn and Mo contributed the most to the positive and negative effects, with weights of 0.421 and 0.467, respectively. The overall effect OR and 95% CI was 0.968 (0.816–1.147) (P = 0.70). The results of BKMR showed consistency. The effect of urinary Zn and Mo on MHO was mediated by inflammatory markers to different degrees (P mediation < 0.05).
Conclusions
(1) Zn and Mo dominate the effects of mixed metal exposure on MHO. Increased urinary Zn and decreased Mo levels were associated with an increased risk of MHO.
(2) PLT, NEU, LYMPH, MON, SII, SIRI, and AISI may play a mediating role in the effects of urinary Zn and urinary Mo on MHO.