A08: Functional impact of genetic risk factors for disease progression within the gut-liver axis
Metabolic liver disease is a rising epidemic following the expansion of obesity in all parts of the world. Disease progression is associated with changes in intestinal microbiota as well as intestinal barrier function, suggesting a role for the gut-liver axis in metabolic liver disease.
Patatin-like phospholipase domain-containing protein 3 (Pnpla3) is a triacylglycerol lipase active in several cells involved in lipid metabolism, such as hepatocytes. A Pnpla3 polymorphism at position 148 is a well-established risk factor for metabolic liver disease.
In this project we will
- use a genetic mouse model carrying the PNPLA3 polymorphism to experimentally dissect the contribution of the intestinal microbiota, diet, alcohol and gut barrier integrity to liver disease.
- translate the experimental observations into the human situation and correlate them to clinical observations and outcomes in patients with PNPLA3 mutations.