PFAS and Potential Adverse Effects on Bone and Adipose Tissue Through Interactions With PPARγ

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a widely dispersed, broad class of synthetic chemicals with diverse biological effects, including effects on adipose and bone differentiation. PFAS most commonly occur as mixtures and only rarely, if ever, as single environmental contaminants. This poses significant regulatory questions and a pronounced need for chemical risk assessments, analytical methods, and technological solutions to reduce the risk to public and environmental health. The effects of PFAS on biological systems may be complex. Each may have several molecular targets initiating multiple biochemical events leading to a number of different adverse outcomes. An exposure to mixtures or coexposures of PFAS complicates the picture further. This review illustrates how PFAS target peroxisome proliferator–activated receptors. Additionally, we describe how such activation leads to changes in cell differentiation and bone development that contributes to metabolic disorder and bone weakness. This discussion sheds light on the importance of seemingly modest outcomes observed in test animals and highlights why the most sensitive end points identified in some chemical risk assessments are significant from a public health perspective.