WP2

Lead Beneficiary: BfR / Braeuning
Co-lead : VU / Leonards
Duration: Months 1 – 48

Objectives

To clarify mechanistic events involved with metabolic outcomes that have been observed in experimental models following PFAS exposure and that are suspected to occur in human populations. The studies will focus on the impact of PFAS on cholesterol homeostasis and on steroid metabolism. Markers of metabolic and endocrine disturbances will be identified in human samples. By taking advantage of blood samples from several cohort studies, PFAS blood serum levels will be correlated with effects on gene expression and metabolomic profiles and finally with adverse outcomes such as cardiovascular disease or obesity. These data, combined with a comprehensive characterization of exposure media and transcriptomic and metabolomics data, will provide a comprehensive understanding of human exposure and effect biomarkers, and new understanding of mechanisms of action. In parallel, human hepatocyte and adipocyte differentiation models will be employed to verify these disturbances in experimental models and to study PFAS-mediated effects on specific molecular endpoints such as nuclear receptor activation or cholesterol and steroid metabolism.