<b>THE ROLE OF </b><b><i>BALDSPOT/ELOVL6 </i></b><b> IN METABOLIC STATES WHEN EXPOSED TO DIETARY STRESS USING A </b><b><i>DROSOPHILA MELANOGASTER </i></b><b>MODEL</b>

<p dir="ltr">Metabolic diseases are a growing concern in the United States, taking up 90% of annual healthcare costs. Understanding the biological pathways that influence the development and outcomes of these diseases is crucial for developing more effective treatments. Recent research has focused on the role of endoplasmic reticulum (ER) stress. Constant ER stress activates the unfolded protein response (UPR), which restores ER homeostasis, but chronic activation results in cell dysfunction and apoptosis. Activation of the UPR is mediated by three ER transmembrane sensors known as PERK, IRE1, and ATF6. Recently it has been shown that reduced expression of an ER-associated fatty acid elongase, ELOVL6, has beneficial effects for physiological parameters related to a variety of ER stress related diseases, such as metabolic diseases, with direct modulation in UPR. For this project, we used a Drosophila melanogaster model to better understand the role of ELOVL6 by reducing the expression of Baldspot, an ortholog to ELOVL6, and measuring physiological parameters with induced metabolic disease. We then looked at UPR and insulin signaling to determine if reduced expression of Baldspot directly influences the ER stress response or other metabolic pathways. Results revealed that in the presence of a high sugar diet with a reduced expression of Baldspot, there is a significant increase in stored fats but no hyperglycemia like that seen in the control group. In addition, reduced expression of Baldspot decreased UPR activation even in the absence of dietary stress indicating metabolic stress isn’t influencing ER stress. It also had no influence on insulin signaling through phosphorylation of protein kinase B (AKT). These results indicate reduced expression of ELOVL6 may have an independent role in regulating overall cellular homeostasis compared to having a role in the ER stress response.</p>