Grant: Project Grant

Diabetes and obesity have reached epidemic levels worldwide. Diabetes is diagnosed when a patient has higher than normal blood glucose level, which is linked to an imbalance in insulin, a metabolically important hormone. A chronic high-fat diet or extended use of anti-inflammatory steroid medications (such as prednisone) can cause obesity and type 2 diabetes. The steroid medication increases blood glucose produced by the liver and causes fat redistribution throughout the body promoting obesity. We are examining new pathways that can contribute to metabolic dysfunction in the liver and fat of animals that are fed a high-fat diet or treated with an anti-inflammatory steroid medication. Our research has uncovered a protein called ARGLU1 that plays an important role transmitting hormone signals to the liver to increase glucose production, without affecting the desired steroid actions on the immune system. ARGLU1 also contributes to signaling activated by fatty acids derived from fat tissue. In this project, we will use mouse models that have ARGLU1 either deleted from the liver, deleted from all fat depots or deleted only from one subtype of fat, to assess the importance of ARGLU1 on whole body metabolism in the context of high-fat diet feeding or anti-inflammatory steroid use. We will use advanced protein and sequencing technologies to uncover the different signalling mechanisms involved. This project has high public relevance because it will allow us to identify new drug targets to benefit patients with obesity and diabetes and potentially identify pathways that can be targeted to allow safer anti-inflammatory steroid drug use for the future.