Presenter: Kacie Brynn Russon
Authors: Kacie Russon, Jordan Davis
Faculty Advisor: Jeffery Tessem
Institution: Brigham Young University
Gut metabolite trimethylamine N-oxide (TMAO) has been frequently associated with chronic diseases such as cardiovascular disease (CVD) and diabetes associated with obesity. A major contributor to the development of type 2 diabetes, is the Endoplasmic Reticulum (ER) stress in β-cells caused by high glucose and fatty acid exposure. Studies have shown TMAO plays a beneficial role in the metabolic processes. Our recent research shows TMAO restores insulin secretion in glucolipotoxic (GLT) conditions, reduces ER stress in the unfolded protein response (UPR) pathway, and normalizes decreased IRE1α protein content that occurs in GLT conditions. It remains to be determined how TMAO directly affects the UPR receptor IRE1α, ER chaperone proteins, and the relationship between IRE1α and insulin secretion. We hypothesize that TMAO alters IRE1α in GLT conditions by directly binding to the protein, TMAO upregulates the expression of ER chaperone proteins, and that IRE1α interaction with TMAO is directly involved in insulin secretion. This project will determine the mechanism by which TMAO protection against GLT occurs in β-cells, furthering our understanding of metabolites in the body. 1. Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends.J Epidemiol Glob Health. 2020;10(1):107-111. doi:10.2991/jegh.k.191028.001 2. Hu FB, van Dam RM, Liu S. Diet and risk of Type II diabetes: the role of types of fat and carbohydrate.Diabetologia. 2001;44(7):805-817. doi:10.1007/s001250100547 3. Dambrova M, Latkovskis G, Kuka J, et al. Diabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels.Exp Clin Endocrinol Diabetes. 2016;124(4):251-256. doi:10.1055/s-0035-1569330 4. Chen S, Henderson A, Petriello MC, et al. Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction.Cell Metab. 2019;30(6):1141-1151.e5. doi:10.1016/j.cmet.2019.08.021