Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent disease impacting around 30% of the US population. Characterized by an increase in hepatic fat, the disease is predicted to become the most prevalent liver disease within a decade. Recent literature has observed changes in copper metabolism with the onset of NAFLD in rodent models. <b>My research seeks to define the connections between copper regulation and NAFLD</b>. This work will facilitate the discovery of biomarkers, diagnostic strategies, and therapeutic interventions for NAFLD and related disorders. A variety of molecular biology techniques have been employed to investigate changes in protein levels, gene expression, and subcellular protein localization. Through protein and gene expression analysis, we have noted an initial state of intracellular copper overload, followed by a decline towards a copper-deficient status over a 24-hour stimulation. Immunofluorescence data, however, shows that despite protein and expression levels reflecting an overall status of copper deficiency, localization of the copper transporter ATP7B is akin to copper overload states. In addition, we have observed non-paradigmatic extracellular copper metabolism. In normal copper export, Cp is secreted in the extracellular media loaded with copper and functions as a copper-dependent enzyme. However, while intracellular data points to increased copper export we found that palmitate stimulation decreased Cp enzyme activity while eliciting no change in Cp concentration. Taken together, our data points to a mechanism wherein palmitate induces a copper imbalance that appears as functional overload, resulting in the cell exporting copper by non-traditional mechanisms towards a copper-deficient state.

Effects of a high fat diet on hepatic copper metabolism

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.