Presenter: Liana Leininger, College of Family, Home, and Social Sciences, Neuroscience
Authors: Jeffery Tessem, Jacob Herring, Kyle Hendricks
Faculty Advisor: Jeffery Tessem, College of Life Sciences, Nutrition Dietetics and Food Science
Institution: Brigham Young University
By the year 2040, an estimated 642 million people are expected to have diabetes globally with the majority having Type 2 Diabetes (T2D). T2D is associated with hyperglycemia, hyperlipidemia and impaired beta cell function. While the effect of hyperglycemia on functional beta cell mass has been studied for years, relatively little is known about the deleterious effects of hyperlipidemia on beta cell function. Recent studies examined the effects of unsaturated fatty acids (UFAs) on beta cell nuclear receptors. Nr4a1, an orphaned member of the nuclear hormone receptor family, is an early-response gene that regulates glucose-stimulated insulin secretion, protects against beta cell apoptosis, and promotes beta cell proliferation, all of which are crucial in maintaining glucose homeostasis. It has been shown that UFAs interact with the ligand-binding domain of Nr4a1 and inhibit Nr4a1 transcriptional activity. However, the mechanism of action has not yet been defined. We hypothesized that decreased Nr4a1 transcriptional activity could be due to UFA induced Nr4a1 degradation or UFA induced changes to Nr4a1 promoter binding. We present data regarding Nr4a1 protein stability and promoter binding in the presence and absence of UFA exposure.