Differential Activation of Peroxisome Proliferator-Activated Receptor Alpha by Per-and Polyfluoroalkyl Substance

PFAS have been shown to activate peroxisome proliferator-activated receptor α (PPARα), a transcription factor involved in lipid metabolism. PFAS comprises a wide range of compounds, and variations in their structural characteristics could reveal important details regarding the level of PPARα activation. Activation and potency were compared across and within PFAS classes based on chemical differences. Perfluorocarboxylated ether was found to be the strongest class, while polyfluorotelomer was the weakest, suggesting the importance of structural features in PPARa activation. Perfluorocarboxylates were consistently better PPARα activators than perfluorosulfonates. Comparing within these two classes, the number of perfluorinated carbon atoms better predicted activation than the number of carbon atoms. In the perfluorocarboxylated ether, perfluorocarboxylate, and perfluorosulfonate classes a direct correlation existed between potency and the percentage of PPARα activation (R2 = 0.702). These findings provide new insight regarding distinct chemical characteristics of PFAS compounds which may be better linked to PPARα activation.