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.

Included in

Biology Commons

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.