Disclosing Environmental Ligands of hL-FABP and PPARγ: Should We Re-evaluate the Chemical Safety of Hydrocarbon Surfactants?

Environmental obesogens can cause adverse health effects through activation of peroxisome proliferator-activated nuclear receptor γ (PPARγ). However, only a small portion of PPARγ ligands in the environment have been discovered to date, due to the co-occurrence of thousands of compounds. In this study, protein Affinity Purification with Nontargeted Analysis (APNA) was employed to identify ligands of human liver fatty acid binding protein (hL-FABP) and PPARγ in indoor dust and sewage sludge. A total of 84 features were “pulled out” by His-tagged hL-FABP as putative ligands, among which 13 were assigned as fatty acids and hydrocarbon surfactants. The binding of hydrocarbon surfactants to hL-FABP/PPARγ was confirmed using both recombinant proteins and reporter cells. These hydrocarbon surfactants, along with >50 homologues and isomers, were detected in dust and sludge at high concentrations. Fatty acids and hydrocarbon surfactants explained the majority of hL-FABP (57.7 ± 32.9%) and PPARγ (66.0 ± 27.1%) activities in the sludge. Notably, hydrocarbon surfactants contributed to PPARγ activities at comparable or even higher levels than fatty acids, with alkylbenzene sulfonates being the predominant PPARγ ligands in sludge. This study revealed hydrocarbon surfactants as the predominant synthetic ligands of hL-FABP/PPARγ, highlighting the importance of re-evaluating their chemical safety as putative obesogens.