Perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) alter the blood lipidome and the hepatic proteome in a murine model of diet-induced obesity.
By Marisa Pfohl, Lishann Ingram, Emily Marques, Adam Auclair, Benjamin Barlock, Rohitash Jamwal, Dwight Anderson, Brian Cummings, and Angela L Slitt
October 7, 2020
Perfluoroalkyl substances (PFAS) represent a family of environmental toxicants that have infiltrated the living world. This study explores diet-PFAS interactions and the impact of perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic (PFHxS) on the hepatic proteome and blood lipidomic profiles. Male C57BL/6J mice were fed with either a low-fat diet (10.5% kcal from fat) or a high fat (58% kcal from fat) high carbohydrate (42g/L) diet with or without PFOS or PFHxS in feed (0.0003% w/w) for 29 weeks. Lipidomic, proteomic, and gene expression profiles were determined to explore lipid outcomes and hepatic mechanistic pathways. With administration of a high fat high carbohydrate (HFHC) diet, PFOS and PFHxS increased hepatic expression of targets involved in lipid metabolism and oxidative stress. In the blood, PFOS and PFHxS altered serum phosphatidylcholines, phosphatidylethanolamines, plasmogens, sphingomyelins, and triglycerides. Further, oxidized lipid species were enriched in the blood lipidome of PFOS and PFHxS treated mice. These data support the hypothesis that PFOS and PFHxS increase the risk of metabolic and inflammatory disease induced by diet, possibly by inducing dysregulated lipid metabolism and oxidative stress.