Perfluorooctanesulfonic acid (PFOS) administration shifts the hepatic proteome and augments dietary outcomes related to hepatic steatosis in mice
Document Type
Article
Date of Original Version
12-1-2020
Abstract
Hepatic steatosis increases risk of fatty liver and cardiovascular disease. Perfluorooctanesulfonic acid (PFOS) is a persistent, bio-accumulative pollutant that has been used in industrial and commercial applications. PFOS administration induces hepatic steatosis in rodents and increases lipogenic gene expression signatures in cultured hepatocytes. We hypothesized that PFOS treatment interferes with lipid loss when switching from a high fat diet (HFD) to a standard diet (SD), and augments HFD-induced hepatic steatosis. Male C57BL/6 N mice were fed standard chow diet or 60% kCal high-fat diet (HFD) for 4 weeks to increase body weight. Then, some HFD mice were switched to SD and mice were further divided to diet only or diet containing 0.0003% PFOS, for six treatment groups: SD, HFD to SD (H-SD), HFD, SD + PFOS, H-SD + PFOS, or HFD + PFOS. After 10 weeks on study, blood and livers were collected. HFD for 14 weeks increased body weight and hepatic steatosis, whereas H-SD mice returned to SD measures. PFOS administration reduced body weight in mice fed a SD, but not H-SD or HFD. PFOS administration increased liver weight in H-SD + PFOS and HFD + PFOS mice. PFOS increased hepatic steatosis in H-SD and HFD groups. Hepatic mRNA expression and SWATH-MS proteomic analysis revealed that PFOS induced lipid and xenobiotic transporters, as well as metabolism pathways. Overall, the findings herein suggest that PFOS treatment did interfere with lipid loss associated with switch to a SD and similarly augmented hepatic lipid accumulation in mice established on an HFD.
Publication Title, e.g., Journal
Toxicology and Applied Pharmacology
Volume
408
Citation/Publisher Attribution
Marques, Emily, Marisa Pfohl, Adam Auclair, Rohitash Jamwal, Benjamin J. Barlock, Ferass M. Sammoura, Michael Goedken, Fatemeh Akhlaghi, and Angela L. Slitt. "Perfluorooctanesulfonic acid (PFOS) administration shifts the hepatic proteome and augments dietary outcomes related to hepatic steatosis in mice." Toxicology and Applied Pharmacology 408, (2020). doi: 10.1016/j.taap.2020.115250.