Breakthrough in the race to cure fatty liver disease that could also cut the risk of Alzheimer’s and depression

A cure for fatty liver disease, a condition caused by overindulging in rich foods, could be seen after a breakthrough in understanding how it damages the brain.

The disease affects one in four adults and children and increases the risk of developing dementia and depression by up to 40 per cent.

Scientists are now working on developing treatments that are expected to work by treating, preventing or reversing fatty liver disease which, in turn, would reduce the risk of developing brain diseases, the researchers said.

However, they warned that it would be more than five years before any drug was ready for a clinical trial and at least a decade before it became available on the NHS – with no guarantee of success.

“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 Anna Hadjihambi, of King’s College. London, who led the study published in The Journal of Hepatology.

“This research emphasizes 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 reduce the risk of developing conditions such as depression and dementia during ageing, when we brain becomes even more fragile,” she said.

Until very recently non-alcohol fatty liver disease (NAFLD), as it is officially known, had been considered a very mild disease.

Now, researchers have demonstrated a direct link between fatty liver disease and the development of neurological conditions.

They discovered that an accumulation of fat in the liver causes a decrease in oxygen to the brain and inflammation to the brain tissue – both of which have been proven to lead to the onset of severe brain diseases.

Researchers have also identified a protein called MCT1 that plays a key role not only in the development of fatty liver disease but also in associated brain diseases.

They’re now working to develop a drug that curbs the activity of the gene that generates the protein.

MCT1 is involved in the chemical reactions that release energy needed by various cells to function.

The researchers specially bred mice to have lower levels of protein and found that they had no fat accumulation in the liver – although they did in their bodies – and showed no sign of brain dysfunction when given the same fat and sugar rich diet that caused fatty liver. disease, anxiety and depression in mice.

This suggests that a drug that can produce the same dampening effect on the MCTI gene could be very effective at preventing and even reversing NAFLD and, in turn, reducing the risk or slowing down the progression of Alzheimer’s and depression.

However, curing fatty liver disease would not reverse Alzheimer’s, researchers said.

There is currently no medical treatment for fatty liver disease. It can be reversed through exercise and healthier eating, but this is difficult to achieve, said Dr. Hadjihambi.

It was already known that people with fatty liver disease were at a higher risk of dementia, but it was thought this could be related to obesity, which usually affects people with the disease.

This study shows, for the first time, that fatty liver disease – and not just obesity – affects the brain and how.

We don’t have a treatment for Alzheimer’s here. But having a target for treating, preventing or reversing the liver disease would mean we are also able to protect their brain in the short and long term,” said Dr Hadjihambi, who will begin further trials in mice next year.

“By focusing on protecting the liver, we will protect the brain and hopefully reduce the number of people with these other serious brain diseases.

“We were able to show that fat in the liver is a crucial driver of the brain dysfunction/deterioration – and therefore lean people with fatty liver might also be at risk.”

Co-author, Professor Luc Pellerin, of the University of Poitiers in France, added: “Identifying MCT1 as a key element in the development of both NAFLD and its associated brain dysfunction points to a possible therapeutic target.”

Experts not involved in the study welcomed its findings.

Fiona Harrison, associate professor at the Vanderbilt University Medical Center in Nashville, said: “This study is very exciting because it identifies a new pathway that could be exploited to design new treatments to prevent or mitigate signs of Alzheimer’s disease.”

Manuel Romero-Gomez, Professor of Medicine at the University of Seville, Spain, said: “These findings are extremely important and is of special relevance, given the current pandemics on obesity, metabolic syndrome and therefore NAFLD.

Thanks to this study, MCT1 has been pointed out as a preventive therapeutic target for NAFLD and liver-related complications. Thus, NAFLD is not just a liver-related disease but also a brain disorder, and the early diagnosis and preventive strategies are much needed. The awareness of this situation is of vital importance for clinicians, in order to adapt and customize the follow-up strategies in NAFLD patients to improve brain health in NAFLD patients.”

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 brain problems. However, it does highlight the need for more research to investigate the relationship between brain health and NAFLD.

“The study also adds 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.”

Professor Debbie Shawcross, who works at King’s College London but wasn’t involved in the study, said: “By examining how the liver communicates with the brain, this ground-breaking study sheds new light on why patients with liver disease – and especially non- – alcoholic fatty liver disease – have a higher likelihood of developing depression and are more likely to report short-term memory loss and cognitive impairment. This is a really important and exciting development, as these findings may point to a potential treatment target.

“The study also provides new evidence as to why cutting down the amount of sugar and fat in our diets is not only important for tackling obesity, but also for protecting the liver and reducing the risk of developing dementia and degenerative brain diseases later in life.” .”

What is non-alcoholic fatty liver disease, how do you get it and what can you do about it at the moment?

Non-alcoholic fatty liver disease (NAFLD) – or just fatty liver disease – is caused by eating too much sugar and fat, with more than 80 per cent of those who are morbidly obese having it.

It is the term for a range of conditions caused by a build-up of fat in the liver and, apart from the emerging evidence of its effect on the brain, there is more longstanding evidence that it can lead to serious liver damage, including cirrhosis. , if it gets worse.

Having high levels of fat in the liver is also associated with an increased risk of serious health problems, such as diabetes, high blood pressure and kidney disease.

“Currently there are no treatments available and the most effective way to reverse NAFLD are lifestyle interventions of healthy diet and exercise,” says Dr Hadjihambi.

However, she cautions that for many people this can be tough.

It really varies between people. In theory, people who lose excess weight can also remove the fat from their liver and reverse the disease. What is difficult is that people who have been overweight for years might lose weight but not be able to sustain this lifestyle and end up putting on the weight again, which is very common.

Also, currently the most common age of diagnosis is 50 years old. Naturally our risk of NAFLD increases with ageing, our metabolism slows down, we are not able to exercise as much and so this makes it hard to lose the weight or reverse the disease. It is possible though and most people can do it if their body allows (depends on age, disability, metabolism, sleeping habits and so on). This also applies to people who are not obese and have NAFLD – a change in their diet and exercise might help most of the time.

The NHS recommends people with NAFLD:

  • Lose weight – you should aim for a BMI of 18.5 to 24.9 (use the BMI calculator to work out your BMI); Losing more than 10 percent of your weight can remove some fat from the liver and improve NASH if you have it
  • Eat a healthy diet – try to have a balanced diet high in fruits, vegetables, protein and carbohydrates, but low in fat, sugar and salt; Eating smaller portions of food can help, too
  • Have water instead of sweet drinks
  • Exercise regularly – aim to do at least 150 minutes of moderate-intensity activity, such as walking or cycling, a week; All types of exercise can help improve NAFLD, even if you don’t lose weight
  • Stop smoking – if you smoke, stopping can help reduce your risk of problems such as heart attacks and strokes

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