Date of Award
12-2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biological Sciences
Committee Chair/Advisor
William S. Baldwin
Committee Member
Lisa Bain
Committee Member
Charles Rice
Committee Member
Joanna Fiddler
Abstract
Disruption of fat metabolism is a hallmark of metabolic disease. A liver enzyme, Cytochrome P450 2B6 (CYP2B6) is an anti-obesity enzyme that produced several omega-3 and omega-6 fatty acid metabolites that could contribute to metabolic diseases such as fatty liver disease. Two of these metabolites, 9-HODE and 9-HOTrE, may be associated with fatty liver. Mice were exposed to 9-HODE and 9-HOTrE to investigate whether they contribute to fatty liver disease under fasting conditions. A transgenic mice model expressing the human enzyme CYP2B6 was also fasted to determine if CYP2B6 leads to increased fatty liver under fasting conditions compared to a mouse model lacking the Cyp2b enzymes. CYP2B6 was found to increase fatty liver under fasting conditions, and female and male mice had significantly different responses.
PFOS, an environmental toxicant, is also associated with metabolic disease. To determine if PFOS causes disruption of metabolism in skeletal muscle, mice or skeletal muscle cells were exposed to PFOS and results from skeletal muscle were compared to a known target of PFOS toxicity, the liver. Skeletal muscle was highly sensitive to PFOS both in mice and cell models, and skeletal muscle showed significant disruption of mitochondrial metabolism, as well as fat and glucose metabolism. Liver was less sensitive and did not show the same changes in metabolism. This demonstrates PFOS significantly affects skeletal muscle metabolism, which can have effects on overall metabolism and metabolic health that can contribute to metabolic diseases.
Recommended Citation
Eccles-Miller, Jazmine Alexis, "Metabolic Dysfunction Caused by Dietary Oxylipins and the Environmental Toxicant PFOS" (2025). All Dissertations. 4103.
https://open.clemson.edu/all_dissertations/4103