# Absorption and Tissue Distribution of Environmental Pollutant HFPO-DA, and Its Effect on Hepatic Lipid Metabolism Reprogramming in Mice

## TL;DR

This study examines how the environmental pollutant HFPO-DA is absorbed and distributed in mice, and how it disrupts liver lipid metabolism.

## Contribution

A reliable method for detecting HFPO-DA in mice and insights into its effects on hepatic lipid metabolism are provided.

## Key findings

- HFPO-DA is rapidly absorbed and distributed in all tested tissues, including crossing the blood–brain barrier.
- HFPO-DA disrupts liver lipid metabolism, causing acylcarnitine accumulation and reduced triglycerides and cholesterol.
- HFPO-DA's long-term effects on the lungs and liver injury are highlighted as areas of concern.

## Abstract

Objective: Hexafluoropropylene oxide dimer acid (HFPO-DA), also known as GenX, is widely used globally, raising concerns about its safety and public health implications. However, its toxicity mechanism remains unclear. The purpose of this study was to develop a reliable method for detecting HFPO-DA in mice and to investigate its absorption, distribution, and impact on hepatic lipid metabolism. Method: HFPO-DA levels were measured in the serum and eight tissues of C57BL/6J mice after oral administration using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Lipid metabolites in the liver were also detected and analyzed. Results: HFPO-DA was rapidly absorbed into the bloodstream and widely distributed throughout all tested tissues. It penetrated the blood–brain barrier, with the highest concentration in the liver; however, long-term effects on the lungs also warrant attention. HFPO-DA disrupted liver lipid metabolism, leading to acylcarnitine accumulation while lowering triglycerides and cholesterol. Conclusion: This study on the pharmacokinetics and tissue distribution of HFPO-DA in mice following oral exposure revealed that HFPO-DA exacerbates liver injury by altering hepatic lipid metabolism. These findings provide theoretical support for toxicological studies on the emerging environmental pollutant HFPO-DA.