Date of Award
8-2024
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological Sciences
Committee Chair/Advisor
William Baldwin
Committee Member
Lisa Bain
Committee Member
Subham Dasgupta
Abstract
Perfluorooctanesulfonate (PFOS) is a persistent environmental pollutant previously used in industrial products such as fire-fighting foams, furniture, and stain-resistant coatings. PFOS is associated with adverse health outcomes, including hepatosteatosis and diabetes. Previously, humanized CYP2B6-transgenic (hCYP2B6-Tg) mice accumulated more PFOS than Cyp2b-null mice and experienced greater mortality; however, the Cyp2b-null mice experienced greater steatosis. Cyp2b-null and hCYP2B6-Tg mice were treated with 0, 1, or 10 mg/kg/day PFOS for 21 days. To determine how PFOS affected the metabolism of polyunsaturated fatty acids (PUFAs) oxylipin concentrations were measured via LC-MS/MS. Additionally, gene expression changes were measured using RNA sequencing. PFOS treatment increased the expression of soluble epoxide hydrolase enzymes which correlated with increased concentrations of diol- and decreased epoxide-containing oxylipins. PFOS-mediated liver toxicity was also associated with perturbed arachidonic acid metabolism. Several hepatic Oatps (Oatp1a4-6) were increased in the hCYP2B6-Tg females compared to the Cyp2b-null females, which may have increased hepatic PFOS uptake and retention.
In addition to altered hepatic lipid metabolism, PFOS-treated Cyp2b-null and hCYP2B6-Tg mice experienced muscle wasting with PFOS. Our lab has previously demonstrated reduced mitochondrial capacity in PFOS-treated C2C12 cells, so we wanted to determine if mitochondrial function was affected in the Cyp2b-null and hCYP2B6-Tg skeletal muscle. We performed Respirometry in Frozen Samples (RIFS) assay to measure mitochondrial complex function. PFOS decreased complex I and IV function. The purpose of this study is to elucidate PFOS’ mechanism of hepatic retention, characterize how it changes PUFA metabolism and its effect on skeletal muscle metabolism.
Recommended Citation
Williams, Lanie, "PFOS Alters Metabolism in the Liver and Skeletal Muscle of CYP2B-Null and Humanized CYP2B6-Transgenic Mice" (2024). All Theses. 4331.
https://open.clemson.edu/all_theses/4331