Exploring the connection between organophosphate flame retardants and Hyperlipidemia: an integrated analysis using NHANES (2011–2018), network toxicology, and mendelian randomization
An association between OPFRs exposure and hyperlipidemia is supported and a potential multi-target, multi-pathway regulatory mechanism is suggested, which suggests a potential multi-target, multi-pathway regulatory mechanism.
Abstract
Organophosphorus flame retardants (OPFRs) are ubiquitous contaminants associated with metabolic disorders. This study examined the association between human exposure to OPFRs and hyperlipidemia and explored potential underlying biological mechanisms. Using data from 3,228 adults from the NHANES cycles of 2011–2018, we analyzed associations using weighted multiple logistic regression, restricted cubic spline analysis, and weighted quantile sum regression. Results showed a robust positive association between urinary OPFRs metabolite levels and hyperlipidemia (OR = 1.33, 95% CI: 1.15–1.55, P < 0.01). Cumulative exposure to OPFRs mixtures was also significantly associated with hyperlipidemia (OR = 1.27, 95% CI: 1.09–1.47, P = 0.002). Subsequent network toxicology and Mendelian randomization analyses suggested that OPFRs may be associated with hyperlipidemia by potentially regulating key targets (e.g. TP53, STAT3, AKT1) and activating specific pathways, including those involved in cancer and the PI3K-Akt signaling cascade. This study supports an association between OPFRs exposure and hyperlipidemia and suggests a potential multi-target, multi-pathway regulatory mechanism.
TDCIPP exposure induced hepatotoxicity in mice, and may induce hepatic lipid toxicity in mice, indicating that the non-cancer risk of BDCIPP should be of concern.
Prenatal TBEP exposure was associated with greater behavioral problems in early childhood, and Alter neonatal gut microbiota and related metabolic pathways may partly underlie this association.
Yuhan Zhou, Liyi Zhang, Qiang Li et al.· Environmental Research· 0 citations
Chronic OP exposure, reflected by these indirect urinary biomarkers, is associated with increased mortality, with heightened vulnerability in younger adults, and underscore the need for stricter pesticide regulation and targeted public health interventions.
Ya-Qian Xu, Yaowen Nuo, Linghui Cai et al.· Chemical Research in Toxicol...· 0 citations
Prenatal exposure to OPFRs and OPPs was associated with smaller left ventricular structural measures in early childhood, mainly reflected by lower left ventricular volume and mass, with OPFRs emerging as main contributors and stronger associations among girls.
Meng Wang, Xi Zhang, Hualin Wang et al.· Environmental Pollution· 0 citations
BACKGROUND
The association between organochlorine pesticides (OCPs)/synthetic pyrethroids (SPs) and thyroid cancer (TC) remains poorly understood, with metabolic mechanisms unexplored.
METHODS
We conducted a 1:1 age- and sex-matched case-control study (n = 668). Serum levels of 27 target analytes (19 OCPs and 8 SPs) were quantified; subsequent analyses were restricted to 13 compounds (10 OCPs and 3 SPs) with detection frequencies ≥85%. Eight machine learning (ML) algorithms with Shapley Additive Explanations (SHAP) were used to identify key pollutants in the 334 case-control pairs. Untargeted metabolomics was performed in a subset of 50 age- and sex-matched case-control pairs. Mixture effects were assessed by Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression. Furthermore, the Latent Unknown Clustering Integrating Multi-Omics Data (LUCID) model was employed to integrate exposure and metabolic data, enabling the identification of TC patient subgroups and the exploration of underlying metabolic mechanisms.
RESULTS
Participants (mean age 45.2 years, 82.3% female) had serum OCPs at 0.007-0.333 ng/mL and SPs at 0.046-0.095 ng/mL. ML algorithms identified fenpropathrin, β-BHC, cyhalothrin, α-BHC, and p,p'-DDD as the top five contributors to TC. Elevated OCPs/SPs exposure was significantly associated with increased TC risk (WQS: adjusted OR = 1.45, 95%CI = 1.34-2.24, P = 0.019; LUCID: OR = 9.33). Fenpropathrin was the primary contributor (BKMR posterior inclusion probability = 1.00; WQS weight = 67.6%). A total of 45 significant differential metabolites (DMs) were identified (VIP ≥1, P < 0.05, and qualitative level 1). LUCID revealed a distinct TC cluster characterized by upregulated S-sulfo-L-cysteine/adenosine and downregulated 2-hydroxycaprylic acid.
CONCLUSION
OCPs/SPs mixtures, driven by fenpropathrin, disrupt amino acid/nucleotide metabolism while suppressing organic acid metabolism, representing a potential TC-associated metabolic signature.
Fei Wang, Chunxiang Li, Linfang Zou et al.· Environment International· 0 citations