The Impact of High-Resolution LC-MS/MS Detected Environmental Exposures on Obesity: A Study of Cumulative Effects Through Statistical Modeling

Background: Obesity is a major and escalating public health challenge worldwide. Growing evidence implicates environmental chemicals, especially organophosphate flame retardants (OFRs) and per- and polyfluoroalkyl substances (PFAS), as potential obesogens due to their ability to disrupt endocrine function and lipid metabolism. However, data on the association between these chemical mixtures and overweight in Chinese populations-particularly in industrialized regions-are scarce, representing a critical knowledge gap. Methods: ), pair-matched by age and sex. Using high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), we quantified serum concentrations of 202 environmental exposures. Multivariable logistic regression, Weighted Quantile Sum (WQS) regression, and Bayesian Kernel Machine Regression (BKMR) models were employed to assess individual and cumulative associations with overweight, adjusting for key metabolic covariates (eg, blood pressure, lipids, and fasting glucose). Results: fold change| ≥ 1). Ten were elevated in the overweight group, most notably tris(2-butoxyethyl) phosphate (TBOEP; adjusted odds ratio [OR] = 2.40, 95% confidence interval [CI]: 1.79-3.33), 1,3,5-triazine-2,4,6-trione tris(2,3-dibromopropyl) ester (TBC), perfluorooctanoic acid (PFOA), and perfluorobutane sulfonic acid (PFBS). The WQS index reflecting the combined effect of these 13 chemicals was strongly associated with higher odds of overweight (OR = 2.33, 95% CI: 1.77-3.07). BKMR analysis further revealed a non-linear cumulative exposure-response relationship, with maximal risk observed at moderate exposure levels. Conclusion: This study provides robust epidemiological evidence that circulating levels of specific environmental pollutants-particularly TBOEP, PFOA, PFBS, and TBC-are significantly associated with increased likelihood of overweight in a northern Chinese adult population. Our findings highlight the potential contribution of complex chemical mixtures to obesity etiology in rapidly industrializing settings and underscore the need for targeted environmental health interventions.