Presenter: Olivia Egan
Authors: Olivia Grinnell-Egan
Faculty Advisor: Jeffery Tessem
Institution: Brigham Young University
Both forms of diabetes result in decreased functional beta-cell mass, which leads to dysfunctional glucose regulation in the body. Recent studies have examined the impact of unsaturated fatty acids (UFAs) on beta-cell nuclear receptors [1,2]. Nuclear receptor 4a1 (Nr4a1) is an early-response gene that regulates insulin secretion, protects against beta-cell apoptosis, and promotes beta-cell proliferation; all of which are essential to glucose homeostasis. Researchers found that the Nr4a1 ligand-binding domain on the Nerve Growth Factor-Induced Gene-B response element (nbre) can bind to unsaturated fatty acids; effectively blocking Nr4a1-nbre binding [3]. Our aim was to determine if the degree of unsaturation impacted Nr4a1-nbre binding ability. We treated Nr4a1-overexpressing INS-1 cell lysate with 16 carbon chain fatty acids of varying degrees of saturation; then ran luciferase assays on the treated cell lysate where the luciferase plasmid contains the nbreresponse element. Our data demonstrates that the degree of saturation in fatty acids impact Nr4a1-DNA binding and that unsaturated fatty acids tend to inhibit Nr4a1-nbre binding more effectively than saturated fatty acids. Understanding these differences provides insight into Nr4a1-regulated insulin release and beta-cell functionality that can be applied to diabetic individuals.