Grant: Project Grant

Fatty liver disease affects one third of people in North America. The disease has few symptoms, but over time causes irreversible damage to the liver. Fatty liver disease involves both an accumulation of fat and increased inflammation in liver, which combine to cause permanent damage. Having fatty liver disease increases the chance of liver failure and of developing other diseases such as diabetes, heart problems, and cancer since damaged livers release harmful substances (fats, hormones, and inflammatory signals) into the blood. Diets high in fat and/or sugar and low physical activity contribute to the rising number of people afflicted. There is no cure for the disease and diagnosis is difficult, mainly because we do not understand the triggers. We have shown that low levels of a protein called PGC-1alpha in liver may cause or worsen disease and promote cancer, and our new studies will help to understand how this happens. We will investigate how low levels of PGC-1alpha decrease the ability of liver to repair damage and whether we can improve this by increasing the levels of this protein in liver cells. We are also investigating whether a common gene variant in PGC-1alpha is associated with the incidence or severity of the disease in humans. Identifying the cause of fatty liver disease will help to discover ways to diagnosis patients early and to design more effective treatments.