Date of Award
2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biotechnology Science and Engineering
Committee Chair
Bernhard Vogler
Committee Member
Sharifa Love-Rutledge
Committee Member
Pamela Twigg
Committee Member
Ahmed Lawan
Committee Member
Victor Ogungbe
Research Advisor
Bernhard Vogler
Subject(s)
Liver cells, Serum, Lipids--Metabolism, Functional genomics
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, is associated with obesity and type 2 diabetes, and as the prevalence of these conditions increases, the incidence of MASLD is expected to rise. However, the mechanisms that underlie the development of MASLD are complex and incompletely understood. Previous work from our group has indicated that the human leukocyte antigen-F adjacent transcript (Fat10) is overexpressed in the LEW.1WR1 rat model, which develops features of MASLD. The objective of this work was to quantify metabolites associated with MASLD in response to Fat10 overexpression. To achieve this end, we used nuclear magnetic resonance (NMR) spectroscopy to assess a panel of 30 serum metabolites in two populations of insulin-resistant, Fat10-overexpressing LEW.1WR1 rats. The results of these analyses showed changes to lipid metabolism, ketogenesis, and oxidative metabolism in the serum of 17-week-old LEW.1WR1 rats compared to LEW/SsNHsd controls, but no significant changes in the metabolism of 23-week-old LEW.1WR1 rats when compared to Wistar Furth controls. To investigate metabolic changes underlying the development of MASLD, we developed and optimized the in-phase/opposite phase (IPOP) protocol for NMR analysis of 13C-enrichment of metabolites in FL83B hepatocytes. Our results showed that the IPOP method gave results for metabolite concentrations that were comparable to traditional NMR metabolomics methods. Furthermore, the IPOP method gave results for 13C-enrichment that improved on these methods. Thus, in the future, this method could be used to measure the 13C-enrichment in metabolites in response to Fat10-overexpression.
Recommended Citation
Hunt, Emily C., "Quantitative metabolomics and ¹³C-enrichment analysis of the effects of Fat10 overexpression on serum and hepatocytes" (2026). Dissertations. 507.
https://louis.uah.edu/uah-dissertations/507