Non-alcoholic fatty liver disease (NAFLD), a condition where there is a build-up of fats in the liver, causes a reduction in oxygen supply to the brain and inflammation of brain tissue. However, partial inactivation of MCT1 is thought to protect against the disease and the associated brain dysfunction.
Fatty Liver Disease
Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease is a form of fatty liver disease. Regardless of alcohol consumption, this metabolic syndrome – which affects more than 80% of morbidly obese people – involves two or more of the following conditions:
- High blood pressure
- High blood sugar
- High triglycerides (fats),
- Low levels of good cholesterol (HDL)
Researchers at the Roger Williams Institute of Hepatology which is affiliated with King’s College London and the University of Lausanne have built on previous work in a new study investigating the link between Non-alcoholic fatty liver disease and brain dysfunction, shedding light on the pathophysiology of the liver-brain axis. The results, published in the Journal of Hepatology, show that the accumulation of fats in the liver causes oxygen deprivation and brain tissue inflammation, which can lead to serious brain diseases.
Mice fed special diets were divided into two groups. Half of the mice were given a 55% fat diet, while the other half of the mice were given a diet containing up to 10% fat.
Oxygen deficiency and brain dysfunction
The researchers compared the effects of the two diets on the liver and brain after 16 weeks. All the mice on the high-fat diet were obese and suffered from Non-alcoholic fatty liver disease, insulin resistance, and brain dysfunction. To explain the latter, the researchers measured tissue oxygenation, cerebrovascular reactivity, and brain blood volume.
It is known that the brain needs a constant supply of oxygen and energy substrates to function. The brain’s blood vessels are well adapted for this and additional mechanisms have been developed to tightly regulate blood flow and adjust oxygen supply according to demand. Therefore, “any change in these mechanisms or in the structure of the cerebral vasculature could have detrimental effects on the oxygenation of brain tissue and overall physiology,” the study authors write.
Mice on a high-fat diet exhibited signs of oxygen deprivation in the brain. Non-alcoholic fatty liver disease reduced both the density and thickness of blood vessels, impairing oxygen delivery to brain tissues. Additionally, brain inflammation caused by the disease could lead to increased oxygen consumption. These mice were also more anxious and showed signs of depression.
MCT1 a potential therapeutic target for the prevention or treatment of Non-alcoholic fatty liver disease
Mice on the low-calorie diet did not show any of the above problems. However, the researchers identified a potential therapeutic target for Non-alcoholic fatty liver disease. The MCT1 protein (Monocarboxylate Transporter 1) specializes in the transport of energy substrates used by different cells to carry out their functions. Giving mice consuming the same high-fat diet lower than normal levels of this protein protects them from Non-alcoholic fatty liver disease and related brain disorders.
Final thoughts
Until an effective and targeted treatment for NAFLD is found, consuming an appropriate diet and exercising can still improve the biomarkers of the condition.
References
Hadjihambi, A., Konstantinou, C., Klohs, J., Jalan, R., Paolicelli, R. C., & Pellerin, L., et al. (2023). Partial MCT1 invalidation protects against diet-induced non-alcoholic fatty liver disease and the associated brain dysfunction. Journal of Hepatology, 78(1), 180–190. https://doi.org/10.1016/j.jhep.2022.09.013
