Actions for Palmitate Mediated Induction of Tryptophan Transaminase Activity Enhances Hepatic Aryl Hydrocarbon Receptor Activation : A Model of NAFLD-Associated AHR Activation
Palmitate Mediated Induction of Tryptophan Transaminase Activity Enhances Hepatic Aryl Hydrocarbon Receptor Activation : A Model of NAFLD-Associated AHR Activation
- Author
- Wolfe, Hannah
- Published
- [University Park, Pennsylvania] : Pennsylvania State University, 2024.
- Physical Description
- 1 electronic document
- Additional Creators
- Perdew, Gary H. and Schreyer Honors College
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- honors.libraries.psu.edu , Connect to this object online.
- Restrictions on Access
- Open Access.
- Summary
- Non-alcoholic fatty liver disease affects millions of people worldwide. The characteristic dysregulated accumulation of hepatic lipid (steatosis) is multi-factorial and promotes progression to cirrhosis and liver failure. Additionally, hepatic steatosis is a contributing factor towards comorbidities including hepatocarcinoma, inflammation and metabolic syndrome, such as type 2 diabetes and obesity. Ligand activation of the aryl hydrocarbon receptor (AHR) is recognized as a contributing component to both the development and maintenance of hepatic steatosis. Importantly, non-xenobiotic, physiological AHR activation is believed to be homeostatically regulated by an expansive reservoir of diet, microbial, and endogenously generated metabolites derived from the amino acid tryptophan. Studies have revealed that lipid loading and steatosis is associated with altered tryptophan metabolism, specifically tryptophan transamination mediated metabolism. Tryptophan transamination, through several transaminases generates indole-3-pyruvate, a key potential metabolic route to AHR activation. Here, we have utilized a cell culture-based model of lipid loading, combined with mRNA, protein and metabolomic analysis, to investigate the effect of the fatty acid palmitate upon tryptophan transaminase expression and downstream AHR activity. Data presented will demonstrate that non-xenobiotic, endogenous AHR activation derived from palmitate-mediated changes in tryptophan metabolites may contribute to the pathophysiology of hepatic steatosis.
- Other Subject(s)
- Genre(s)
- Dissertation Note
- B.S. Pennsylvania State University 2024.
- Technical Details
- The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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