Research shows fatty liver disease may endanger brain health

Posted on: 15th December 2022

In a study examining the potential link between non-alcoholic fatty liver disease (NAFLD) and brain dysfunction, scientists at the Roger Williams Institute of Hepatology, affiliated to King’s College London and the University of Lausanne, found an accumulation of fat in the liver causes a decrease in oxygen to the brain and inflammation to brain tissue – both of which have been proven to increase the risk of developing brain diseases when they persist chronically.

Several studies have reported the negative effects of an unhealthy diet and obesity can have on brain function however this is believed to be the first study that clearly links NAFLD with brain deterioration and identifies a potential therapeutic target.  While this area of research is important, it is at an early stage and yet to be applied in a human setting.

Pamela Healy, Chief Executive of the British Liver Trust said, “These results may worry and concern people who have been diagnosed with NAFLD and it’s important that we put this in context. Not all people living with NAFLD will experience depression or other brain problems and further research is needed to investigate the relationship between brain health and NAFLD.  The study does add to the growing body of evidence about the importance of maintaining a healthy weight and reducing the amount of fat and sugar that we consume. This advice is not only important for keeping our livers healthy but also for maintaining our cognitive function.

It's also important that we recognise that addressing this is not just down to individuals but is a public health issue – we have created an environment where being overweight is the norm. The government must urgently tackle the accessibility and abundance of unhealthy food which is significantly cheaper than healthy alternatives.  This has to start with reinstating plans to restrict multibuy deals and advertising of unhealthy foods with immediate effect.”

The research, conducted in collaboration with Inserm (the French National Institute of Health and Medical Research) and the University of Poitiers in France, involved feeding two different diets to mice. Half of the mice consumed a diet with no more than 10% fat in their calorie intake, while the other half’s calorie intake contained 55% fat; intended to resemble a diet of processed foods and sugary drinks.

After 16 weeks researchers conducted a series of tests to compare the effects of these diets on the body and more specifically, on the liver and the brain. They found that all mice consuming the higher levels of fat were considered obese, and developed NAFLD, insulin resistance and brain dysfunction.

The study which was funded by the University of Lausanne and Foundation for Liver Research, published today in The Journal of Hepatology, also showed that the brain of mice with NAFLD suffered from lower oxygen levels. This is because the disease affects the number and thickness of the brain blood vessels, which deliver less oxygen to the tissue, but also due to specific cells consuming more oxygen while the brain is becoming inflamed. These mice were also more anxious and showed signs of depression, with no severe changes in their ability to learn and memorise certain tasks.

By comparison, the mice consuming the healthy diet did not develop NAFLD or insulin resistance, they behaved normally, and their brain was completely healthy.

“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.

To try and combat the negative effect that NAFLD has on the brain, the scientists bred mice with lower levels of a whole-body protein known as Monocarboxylate Transporter 1 (MCT1) – a protein specialised in the transport of energy substrates used by various cells for their normal function.

When these mice were fed the same unhealthy fat- and sugar-rich diet as those in the initial experiment, they had no fat accumulation in the liver and exhibited no sign of brain dysfunction – they were protected from both ailments.

“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.”

The full paper is available to view online in The Journal of Hepatology.