By connecting the dots between chronic drinking, molecular clocks, and energy storage patterns, UAB doctoral student Uduak Udoh has identified a potential new approach to target alcoholic liver disease. The work has also earned her a top honor from the Research Society on Alcoholism (RSA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and kudos from former NIAAA director Enoch Gordis, M.D.
Udoh, a fifth-year doctoral student in Pathobiology and Molecular Medicine, received the Enoch Gordis Research Recognition Award during the RSA's annual scientific meeting this summer. At the meeting, she presented results from her dissertation project, "Hepatic Glycogen Metabolism Is Impaired by Alcohol Consumption: Possible Role of the Liver Molecular Clock."
Liver cells, like almost all human cells, have a built-in circadian clock—a set of genes that control metabolism and other biological processes in a daily cycle. Udoh's research shows that chronic alcohol consumption disrupts the liver's normal pattern of creating glycogen, a storage form of glucose.
"Glycogen in the liver is an important fuel reserve that the body uses in between fasting and eating," explains Udoh, who is a member of the lab of Shannon Bailey, Ph.D., in the Division of Molecular and Cellular Pathology. Previous research has shown that the liver clock controls glycogen synthesis in a regular rhythm throughout the day. Emerging studies show that alcohol can disrupt the liver clock's timing, just as it disturbs the main circadian clock in the brain to disturb sleep and other behaviors.
Udoh's work connects these two observations. In mouse models, "we normally see a nice diurnal rhythm to glycogen content in the liver, which makes sense because metabolic needs vary throughout the day," Udoh says. But chronic alcohol consumption brings a significant change in that pattern, and a corresponding decrease in glycogen levels, Udoh found. She also demonstrated that alcohol disrupts signaling genes and proteins regulated by the liver clock that control glycogen metabolism.
Without sufficient glycogen, the liver may lack the energy to repair alcohol-generated damage, contributing to alcoholic liver disease. Ultimately, Udoh's research "highlights the molecular clock as a novel therapeutic target for alcoholic liver disease," says Bailey. (Learn more about Bailey’s own research into chronic alcohol consumption and the liver clock in this Mix podcast.)
Udoh's work was one of only six selected for presentation at the Research Society on Alcoholism meeting from hundreds of applications. Judges selected her for the Gordis award, which recognizes outstanding research among graduate students and postdoctoral fellows, based on her oral presentation and research poster session. One of the highlights of the event was discussing her work with Dr. Gordis himself, Udoh says. "It's a great honor."