Brain health is negatively impacted by fatty liver disease: Study

In a study examining the connection between non-alcoholic fatty liver disease (NAFLD) and brain dysfunction, researchers at the Roger Williams Institute of Hepatology, affiliated with King’s College London and the University of Lausanne, found that an accumulation of fat in the liver results in a reduction in oxygen to the brain and inflammation of brain tissue, both of which have been linked to the onset of severe brain diseases. NAFLD affects more than 80% of morbidly obese patients and around 25% of the general population.

This study is thought to be the first to definitively correlate NAFLD with brain degradation and identify a possible treatment target. Several studies have documented the detrimental impact that an improper diet and obesity may have on brain function. Inserm, the French National Institute of Health and Medical Research, and the University of Poitiers collaborated on the study, which entailed giving mice two alternative diets. A diet meant to imitate one made up of processed foods and sugary drinks was given to one half of the rats, while the other half received calories that were 55% fat.

Researchers compared these diets’ effects on the body, and more especially, on the liver and the brain, after 16 weeks of testing. All of the mice who consumed the greater amounts of fat were discovered to be obese, have NAFLD, insulin resistance, and cognitive impairment. The University of Lausanne and Foundation for Liver Research-funded study also revealed that mice with NAFLD had reduced oxygen levels in their brains. This is owing to the disease’s effects on the quantity and thickness of brain blood arteries, which reduce the amount of oxygen delivered to the tissue, as well as the fact that some cells demand more oxygen when the brain is inflamed.

Additionally, these mice displayed depressive symptoms and were more agitated.
In contrast, the mice on the healthy diet did not have NAFLD or insulin resistance, exhibited normal behaviour, and had a fully functional brain.

“It is very concerning to see the effect that fat accumulation in the liver can have on the brain, especially because it often starts off mild and can exist silently for many years without people knowing they have it,” said lead author Dr Anna Hadjihambi, sub-team lead in the Liver-Brain Axis group at the Roger Williams Institute of Hepatology and honorary lecturer at King’s College London.

Monocarboxylate Transporter 1 (MCT1), a protein that specialises in the transfer of energy substrates utilised by numerous cells for their appropriate function, was bred into mice with lower amounts in an effort to counteract the harmful effect that NAFLD has on the brain. These mice were protected against both diseases when given the same unhealthy diet high in fat and sugar as those in the previous trial. They showed no signs of brain malfunction and did not accumulate fat in the liver.

“Identifying MCT1 as a key element in the development of both NAFLD and its associated brain dysfunction opens interesting perspectives,” said Professor Luc Pellerin, director of the Inserm U1313 research unit at the University of Poitiers in France and senior researcher in the study. “It highlights potential mechanisms at play within the liver-brain axis and points to a possible therapeutic target.”

Dr Hadjihambi added: “This research emphasises that cutting down the amount of sugar and fat in our diets is not only important for tackling obesity, but also for protecting the liver to maintain brain health and minimise the risk of developing conditions like depression and dementia during ageing, when our brain becomes even more fragile.