Effects of Per- and Polyfluorinated Alkyl Substances (PFAS) on Amphibian Body Condition: Is Altered Lipid Metabolism The Driver?

Per- and polyfluoroalkyl substances (PFAS) are globally distributed contaminants with widespread use in commercial and consumer products. Due to their aquatic and terrestrial life cycle, amphibians are particularly susceptible to sublethal effects of PFAS exposure and are regularly exposed in the field. In amphibians experimentally-exposed to PFAS, body condition, measured using the scaled mass index (SMI), is often affected. In vitro and rodent studies have demonstrated that PFAS can alter lipid metabolism, but whether changes in fat stores can explain previously observed PFAS-mediated changes in amphibian SMI remains unexplored. Because lipids are a primary fuel for anuran metamorphosis and reproduction, understanding whether altered lipid metabolism can explain previously observed effects on SMI is critical. The objective of this work is to determine whether PFAS alter lipid deposition and if this correlates with observed changes in SMI in the amphibian model, Xenopus laevis. Additionally, we will explore changes in gene expression of peroxisome proliferator-activated receptors (PPARs) and associated signaling cascades, which have been hypothesized as mediators of PFAS-induced dysregulation of lipid homeostasis. Our data will aid in mechanistic understanding of PFAS toxicity in amphibians and determine whether Xenopus may be an appropriate model for studying PFAS-mediated lipid homeostasis in vertebrates more broadly