Environ Res. 2026 Apr 5:124437. doi: 10.1016/j.envres.2026.124437. Online ahead of print.
ABSTRACT
Childhood dyslipidemia may predispose individuals to cardiovascular disease later in life. However, evidence linking pesticide exposure to lipid profiles in children, particularly through specific metabolic pathways, is lacking. In a repeated-measures study involving 141 children aged 4-12 years in Guangzhou, China, we assessed 15 urinary pesticide biomarkers and serum lipids over three visits. Untargeted metabolomic profiling was conducted on paired serum and urine samples from a subgroup (48 children with 144 visits) comparable to the overall children. Linear mixed-effects models and weighted quantile sum regression (WQS) were applied to assess the associations of individual and mixed pesticide exposures with serum lipid profiles, respectively. The meet-in-the-middle approach was utilized to identify potential overlapping metabolites and metabolic pathways. Pairwise and dimension-reduction mediation analyses were performed to quantify significant mediating metabolites and pathways. After multiple-testing correction, consistent associations were observed in both the overall children and the metabolomics subgroup: 4-nitrophenol (PNP) was significantly associated with elevated triglycerides (TG), whereas the sum of the molar concentrations of thiamethoxam and its metabolites (ΣTHM) was associated with higher total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C).WQS results revealed a positive association of pesticide mixture with TG, TC, and non-HDL-C, with PNP and ΣTHM emerging as the primary contributors. Urinary tyrosine metabolism and serum sphingolipid, glycerophospholipid, linoleic acid metabolism, and unsaturated fatty acid synthesis significantly mediated pesticide-lipid associations, with mediation proportions ranging from 20.9% to 70.9%. Several individual metabolites within these pathways were identified as significant mediators. Among them, serum SM (d18:1/26:0), serum PE (20:0_18:0) and urinary 3,4-dihydroxybenzeneacetic acid showed the largest mediation proportions in sphingolipid, glycerophospholipid, and tyrosine metabolism, respectively. This study indicates that exposure to selected pesticides in children may be associated with elevated blood lipid, substantially mediated by perturbations in lipid and amino acid metabolism.
PMID:41946438 | DOI:10.1016/j.envres.2026.124437