Superfund Research Program
PFAS Compound Effects on Metabolic Abnormalities in Rodents
In 2019, the Per- and Polyfluoroalkyl Substances (PFAS) Compound Effects on Metabolic Abnormalities in Rodents Project focused on better understanding the impact of developmental and lactational PFAS exposure for risk of hepatic steatosis (i.e., fatty liver) in the context of maternal diet and the impact of emerging PFAS detected in other Center research projects in cryopreserved human hepatocytes on fatty liver endpoints. The researchers have a publication under consideration that requires minor changes (Salter et al., revisions requested, Toxicological Sciences, 2019) and another currently in preparation (Marques et al., 2019). Salter et al., illustrated that PFOS (100 microgram/kg/day) decreased the effects of calorie restriction to induce beneficial pathways that aid the liver in activation of metabolic pathways (i.e., AMP-Activated Kinase, AMPK) and lipid accumulation in mice. Marques et al., illustrated that PFOS (300 microgram/kg/day) augmented high fat diet-induced hepatic steatosis and also dampened the beneficial response of the liver to lose fats with a switch from high fat to a low fat diet. With respect to Aim 1, the researchers have completed all of the proposed PFASs treatments in murine 3T3-L1 adipocytes and have performed proteomic analysis for PFAS that were observed to induced adipogenesis. All proposed human hepatocyte treatments have been conducted and the researchers have worked with other Center research projects to treat hepatocytes with additional PFAS detected in bird, fish, whale livers, as well as PFAS detected in serum samples from the Inflammation and Metabolic Changes in Children Developmentally Exposed to PFAS Project. With respect to Aim 1, the team has completed the proposed developmental PFAS exposures and are currently analyzing necropsy data and tissues. With regard to Aim 3, they have completed PFAS protein binding studies to albumin proteins using complementary biophysical techniques that provide new mechanistic insight into the binding event. The researchers are currently examining PFAS partitioning into biological membranes in collaboration with the Impacts of Geochemistry and Transport on PFAS Exposures from Drinking Water and Fish Project, and assisted these researchers with tissue lipid measurement. Dassuncao et al. (2019) illustrated that both phospholipids and proteins are associated with the PFAS tissue distribution in a marine mammal and that highest concentrations are found in the liver and brain, likely through facilitated transport. They have also forged a collaboration with researchers from the Developing Passive Samplers for the Detection and Bioaccumulation of PFASs in Water and Porewater Project to understand liver lipidomic changes in birds and mice exposed to PFAS.