Grant: Project Grant

Fatty liver disease, known as non-alcoholic fatty liver disease (NAFLD) and recently named metabolic dysfunction-associated steatotic liver disease (MASLD), is a major health problem that is on the rise due to increased obesity and diabetes. It is characterized by liver inflammation and may progress to advanced tissue damage (cirrhosis) and liver failure. The disease presentation and progression are different between men and women and the reason for such differences is not clear. IL22, is a protein (a cytokine) released from a type of white blood cells and a critical mediator of immunity and inflammation. This protein was shown to prevent the development of MASLD. Our research team has demonstrated, in animal and human studies that IL-22 is more protective in females than in males against the development of MASLD. In the current project, we aim at dissecting how IL22 is exerting its protective functions in females. We will evaluate the interactions of IL22 with other regulatory molecules, hormones or the microbiota (the collection of bacteria that naturally live in our bodies), that have been previously shown to influence inflammation and tissue damage in MASLD conditions. We will be using mice with MASLD (fed a high fat diet) which are either genetically normal or modified to lack the expression of the receptor of IL22 or of another molecule of interest to our study. Liver of these mice will be evaluated on a molecular basis using advanced immunological, molecular, and biochemical techniques. Our study will guide future clinical studies testing IL22-based therapeutic approaches in treatment of female versus males with fatty liver disease.