Grant: Project Grant

Our livers are responsible for storing, breaking down, and creating fuels to supply the body in times of energy demand. For example, when we fast, the liver breaks down stored fat and protein, turning them into forms of energy that can be used by other organs. To do this well, the liver listens to signals from many organs and can quickly alter its course when needs change (i.e. after we eat a meal). One way it senses these changes is by using a family of proteins called PGC-1As, which become activated when liver cells sense that other tissues need fuel. We recently found that some PGC-1A family members can also protect liver cells from damage, suggesting that these proteins have multiple important roles. Importantly, levels of PGC-1A in liver are often low in people living with diabetes or steatotic liver disease. Metabolic dysfunction associated steatotic liver disease (MASLD) affects about 25% of the Canadian population. The disease involves a build-up of fat in liver that is believed to cause inflammation and permanent scarring over time. MASLD increases risk of other diseases such as cardiovascular disease and cancer. Notably, 70-80% of people living with diabetes also have MASLD. We have shown that low PGC-1A in liver can worsen MASLD, and our new studies are designed to reveal important role(s) for PGC-1A in controlling energy demand and responses to stress. We will also investigate whether and how disruption of these function contributes to disease. Our project will help us better understand how the liver works, what goes wrong in MASLD, and why it is so closely linked to diabetes, in hopes of finding new ways to prevent, treat and cure these diseases.