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University of Rhode Island

Superfund Research Program

PFAS Compound Effects on Metabolic Abnormalities in Rodents

Project Leader: Angela L. Slitt
Co-Investigator: Geoffrey D. Bothun
Grant Number: P42ES027706
Funding Period: 2017-2022
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Project Summary (2017-2022)

As part of the University of Rhode Island-led Sources, Transport, Exposure and Effects of PFASs (STEEP) Superfund Research Program Center, this project is addressing the emerging problem of poly- and perfluorinated alkyl substances (PFASs) contamination. PFASs are considered emerging environmental pollutants, notably found at high concentrations at sites contaminated by aqueous firefighting foams, such as Cape Cod. Human exposure to PFASs has been linked to immunotoxicity, cancer, as well as metabolic and dyslipidemia. Specific to metabolic disorders, PFASs are known to highly partition to the liver and links have been established between PFAS serum levels, specifically perfluorooctanic acid (PFOA) and perfluorosulfonic acid (PFOS), and liver injury. While insightful, these two common PFASs represent only a fraction of PFASs that exist within the contaminated sites and have been detected in. Understanding the mechanisms driving the biological response to PFASs are still emerging.

STEEP researchers are working to (i) address whether environmental exposure to PFASs contributes an additional increase risk for obesity-induced fatty liver disease and metabolic disorders, and (ii) identify the physicochemical and partitioning behavior of PFASs that contribute to bioaccumulation. The overarching hypotheses are (1) that PFAS exposure increases diet-induced hepatic steatosis and inflammation, which is potentially via increased adiposity and altered adipokine secretion, and (2) that the biological responses (e.g. liver weight) and biomarkers (e.g. oxidative stress gene expression) can be correlated with the protein, lipid, and/or membrane partitioning behavior of PFASs. These hypotheses are being tested by evaluating the potential of PFASs to impact hepatic lipid accumulation, adipogenesis, and adipokine secretion; evaluating postnatal PFAS exposure as an additional risk factor for obesity-induced hepatic steatosis and adipocyte dysfunction; and determining the physicochemical properties of PFASs and their partitioning behavior to fat and in protein phases.

Furthermore, through this project significant gaps in Agency for Toxic Substances and Disease Registry (ATSDR) guidance-related to PFASs are being addressed pertaining to (i) outcomes with early in life PFAS exposure, (ii) mechanistic biomarkers for PFAS exposure in addition to liver endpoints, (iii) risk factors common to the United States population that might impact response to PFAS exposure (i.e. diet; obesity), and (iv) accurate measurements of physicochemical properties that are needed to predict bioaccumulation and toxicity.

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