Exposure to novel brominated flame retardants (NBFRs) drives obesity via PPARγ-mediated adipogenesis: A cross-ethnic study in aging agro-pastoral communities

The global obesity epidemic is increasingly linked to environmental chemical exposure, yet the role of novel brominated flame retardants (NBFRs) remains poorly understood. In this cross-ethnic study of elderly agro-pastoralists in Inner Mongolia, we compared serum NBFRs levels and metabolic biomarkers between Mongolian (n = 30) and Han (n = 47) populations. The Mongolian group, with relatively higher meat/dairy-rich diets, showed significantly higher NBFR concentrations, body mass index (BMI), and low-density lipoprotein cholesterol (LDL-C). Alarmingly, 72.7 % of participants were classified as overweight/obese, far exceeding China’s national average. Serum pentabromotoluene (PBT), pentabromoethylbenzene (PBEB), and pentabromobenzyl acrylate (PBBA) showed significant positive correlations with BMI ( p < 0.05). The quantile G-computation (QGC) model further revealed that PBBA exerted particularly prominent effects on BMI. Strikingly, piecewise regression revealed accelerated NBFRs accumulation in individuals with BMI≥28 ( p < 0.05), indicating a bidirectional “NBFRs-BMI feedback loop”. Molecular docking studies demonstrated that PBBA and PBT exhibit a higher binding affinity to PPARγ than the conventional agonist Rosiglitazone, with specific interactions at key amino acid residues (ARG-288 and ILE-326) on helix H3. These findings suggest that PBBA and PBT may act as novel PPARγ agonists, potentially promoting adipogenesis and consequently leading to weight gain.