Grant: Operating Grant - PA: INMD Start-up Funds (Clinicians and New Investigators)

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 the liver, which combine to cause permanent damage. Having fatty liver disease not only increases the chance of liver failure, but also of developing other diseases such as diabetes and heart problems since a damaged liver releases 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 fatty liver disease and our new studies will help to understand how this happens. We will investigate how low levels of PGC-1alpha decrease the liver's response to insulin and increase inflammation, and whether we can improve the disease by increasing the levels of this protein in liver cells. We are also trying to identify signals released from diseased liver cells that may help us to diagnosis the disease. Identifying the cause of fatty liver disease will help to discover ways to diagnosis patients early and to design more effective treatments.