Therapeutic Effects of Soluble Epoxide Hydrolase Deletion on Non-Alcoholic Fatty Liver Disease (2016)

Undergraduate: Bobbie Nguyen

Faculty Advisor: Craig Lee
Department: Chemistry

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Non-alcoholic fatty liver disease (NAFLD) is an emerging public health problem that affects 20-33% of the world¿¿¿s population. Currently, there are no effective therapeutic treatments for NAFLD and a critical need to identify and research novel therapeutic targets for NAFLD that slow its progression. Initial research has shown that epoxyeicosatrieonic acids (EETs) elicit protective cardiovascular responses, including vasodilation and anti-inflammatory actions. However, under normal circumstances, the soluble epoxide hydrolase (sEH) enzyme rapidly hydrolyzes these EETs into their less biologically active diol metabolites, which do not elicit the same protective responses. As such, inhibition of the sEH enzyme increases levels of EETs within the body and has emerged as a novel therapeutic target for cardiovascular diseases. The purpose of this research project is to investigate the hypothesized therapeutic ability of inhibiting sEH in NAFLD. Using knock-out mice fed a methionine-choline deficient diet (MCD) and a high-fat diet (HFD), we effectively increased the amount of EETs and utilized their protective effects. Specifically, knock-out of the Ephx2 gene that codes for the enzyme significantly reduced hepatic injury and inflammation, glucose intolerance, and fibrosis in both the MCD and obesity models. Collectively, these findings suggest that increasing EET levels through sEH inhibition is a potential therapeutic target for slowing the progression of NAFLD.