Superfund Research Program
PFAS Compound Effects on Metabolic Abnormalities in Rodents
The PFAS Compound Effects on Metabolic Abnormalities in Rodents Project has been evaluating whether per- and polyfluorinated alkyl substances (PFAS) cause fat (adipose) tissue and liver dysfunction in cell-based tests and mouse models and identify correlations between biological endpoints, physicochemical properties, and lipid and protein partitioning behavior. Aim 1 has been testing whether PFASs relevant to the Cape Cod Community can induce murine 3T3-L1 cells to become adipocytes and human hepatocytes to accumulate lipids. Angela L. Slitt, Ph.D., and her research team will be finishing Aim 1 by completing their analysis of transcriptomic and proteomics changes in the cells after PFAS exposure and perform PFAS treatments on human adipose tissue and measuring media adipokine secretion from their cultured adipocyte experiments. Aim 2 will evaluate whether exposure to PFASs early in life through breast milk can increase body measurements associated with obesity and fatty liver disease in laboratory mice. The researchers then plan to conduct the funded rodent study in Year 3, collect tissues, and perform basic analyses on the resulting tissues. Aim 3 will evaluate physicochemical properties of PFASs, how these properties influence partitioning or binding to lipid phases and proteins, and how these properties relate to the activities in cell-based assays in Aim 1. This Project is working with the Inflammation and Metabolic Changes in Children Developmentally Exposed to PFASs Project to ensure overlap of markers of disease to be tested humans will also be tested in mice and the cell-based laboratory tests and that the concentrations of PFASs utilized are relevant to human exposure. This project is working with the Inflammation and Metabolic Changes in Children Developmentally Exposed to PFASs Project to identify overlapping biomarkers for inflammation and metabolic changes in the human epidemiology study and the rodent study. Slitt and her researchers have been testing these emerging laboratory-based tests when possible. Overall, the Project is informing the scientific community about the relative potential of various PFASs to induce metabolic abnormalities in cells and mice and will improve understanding of how the chemical properties of each can contribute to the observed cellular effects.