Grant recipient

Karen Louise Thomsen

Brain dysfunction in non-alcoholic fatty liver disease: Exploring potential mechanisms and treatments

Grant amount: DKK 6,993,900

Non-alcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease. Up to 70% of patients suffer from brain dysfunction with poor outcome and socio-economic impact. NAFLD animals show brain dysfunction and activation of body-wide inflammation and inflammatory cells in the brain. Fat in the liver impairs the normal conversion of nitrogen into urea, causing buildup of the toxin ammonia. A hormone, GLP-1, which is low in NAFLD patients, helps reduce liver fat and brain inflammation. Moreover, abnormal autonomic nervous system signals in NAFLD may add to brain inflammation. We aim to discover if brain dysfunction in NAFLD arises as a consequence of brain inflammation, and if so, what are the potential mechanisms. We will study this: (i) In NAFLD rats and in patients, to ascertain mechanisms using behavioral tests, examinations of liver and brain tissue, and brain imaging, (ii) Experiments targeting therapy to the putative mechanisms (e.g. GLP-1) in rats and as well as in patients.