Brain dysfunction connected to fatty liver disease

Meet Karen Louise Thomsen

“Is brain dysfunction in patients who suffer from non-alcoholic fatty liver disease a consequence of malfunction of the liver and brain inflammation, and if so, what are the potential mechanisms?”

This is an urgent research question for MD, PhD Karen Louise Thomsen, born 1972.

Her research focuses on studying the pathophysiological impact of inflammation on organ injury in liver diseases ranging from liver cirrhosis to alcoholic hepatitis and non-alcoholic fatty liver disease. The latter is caused by the storage of fat in the liver in patients who do not necessarily drink alcohol, but eat unhealthily and exercise too little. As a result it seems that some become forgetful, confused or otherwise cognitively disturbed.

More than one in four is affected

“Alarming increases in obesity and diabetes have contributed to a dramatic increase in the rates of non-alcoholic fatty liver disease in more than one in four people in the western world. 70 percent of them may be affected by impaired cognition, so we have an urgent clinical need for specific targeted interventions,” Karen Louise Thomsen says.

Together with colleagues from University College London she has proved that fat in the liver disturbs a normal conversion of nitrogen into urea, causing buildup of the toxin ammonia. Additionally, her group has made the novel observation that rodents affected by the disease show brain dysfunction as well as activation of systemic inflammation and inflammatory cells in the brain. Next step is to show it in pig models that better resemble human beings.

Targeting therapy, brain imaging and behavioral tests

“We know that a specific hormone, GLP-1, which is reduced in the patients, helps reduce liver fat and brain inflammation. Moreover, abnormal autonomic nervous system signals in the disease may add to brain inflammation. We therefore experiment with specific targeted therapies in rats, pigs as well as in patients,” Karen Louise Thomsen says.

In 2019 she received a 5-year Clinical Emerging Investigator Grant from the Novo Nordisk Foundation to build her own research group to study patients with non-alcoholic fatty liver disease by using behavioral tests, examine liver and brain function, and do brain imaging. All this together with collaborators from Translational Neuropsychiatry Unit and Department of Nuclear Medicine & PET-Centre.

Karen Louise Thomsen and her group is also involved in several studies assessing the clinical progress of patients with liver cirrhosis. Among other things, she is responsible for a new project that investigates the mechanisms and impact of faecal microbiota transplantation:

“The gut microbiota is a driver of complications and disease progression, so it may therefore fundamentally improve the disease progression and prognosis for these patients,” she says.