Researchers from Inserm, the University of Poitiers, King’s College London and the University of Lausanne published in the Journal of Hepatology have for the first time linked non-alcoholic fatty liver disease (NAFLD), caused by excessive consumption of fat and sugar, to neurodegenerative diseases such as dementia. The researchers thus highlight the relationship between the liver and the brain for the proper functioning of brain functions.
Non-alcoholic hepatic stenosis, also known as fatty liver disease, can cause cirrhosis and affects an ever-increasing proportion of the sedentary population and developing obesity problems, 80% of people suffering from morbid obesity are thus concerned. Different studies had already highlighted the effects of an unbalanced diet and obesity on brain function, but the present study is the first to link fatty liver disease to neurological problems in animal models and to identify a potential therapeutic target.
In particular, the scientists found that fatty liver accumulation leads to decreased oxygen to the brain and inflammation of brain tissue, both of which are associated with increased serious neurological risks such as dementia. The study involved feeding mice two different diets, one half given a diet with no more than 10% fat in calories and the other half given a 55% fat caloric intake, comparable to a diet of processed foods and sugary drinks.
After 16 weeks, the scientists conducted tests to compare the effects of the two diets on the body, including the liver and brain. They found that all mice on the high-fat diet were considered obese and had developed non-alcoholic fatty liver disease and insulin resistance. The brains of these mice had lower oxygen levels and marked brain dysfunction was also observed, particularly behavioral problems. The researchers proposed two hypotheses to explain these phenomena: first, the disease would reduce the number and diameter of cerebral blood vessels, bringing less oxygen to the tissues, and second, specific cells could consume more oxygen because of the inflammation detected in the brain.
Mice with these symptoms were also more anxious and showed signs of depression. Anna Hadjihambi, the first author of the study and an honorary lecturer at King’s College, says it’s very worrying to see the effect that fatty liver build-up can have on the brain, especially because this disease is often benign, to begin with, and can exist silently for years without people being aware of it.
To find solutions to the effects of this disease on the brain, scientists bred mice with lower levels of a protein called MCT1 that specializes in transporting energy substrates used by different cells for their normal function. This protein was of particular interest to the researchers because it is involved in different organs involved in the body’s energy balance, including the liver and brain. When this particular population of mice was subjected to the high-fat diet of the first experiment, they did not show any accumulation of fat in the liver or brain dysfunction.
For Luc Pellerin, the last author of the study, the identification of MCT1 highlights the potential mechanisms at play in the liver/brain axis and indicates a possible therapeutic target. This work underlines that reducing fat and sugar consumption does not only help fight obesity but could also protect the liver and thus preserve brain health by minimizing the risk of developing diseases such as depression or dementia as we age.
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