Scientists discovered that a common liver disease called MASLD (metabolic dysfunction-associated steatotic liver disease), which happens when fat builds up in the liver, can actually affect how your brain works and your memory. Using mouse studies, researchers found that when the liver has this disease, it causes problems with memory, movement, and learning. The exciting part? They tested a new treatment that targets the liver and found it could reverse these brain problems. This suggests that fixing the liver might also fix brain issues caused by the disease, opening up new ways to help people with this condition.

The Quick Take

  • What they studied: Whether a fatty liver disease can cause brain and memory problems, and if treating the liver can fix those brain issues
  • Who participated: Laboratory mice that were fed diets to develop fatty liver disease similar to what happens in humans
  • Key finding: Mice with fatty liver disease had memory and movement problems, but when scientists treated their livers with a special therapy, the brain problems went away and brain function improved
  • What it means for you: This research suggests that if you have fatty liver disease, it might be affecting your brain and memory in ways you don’t realize. The good news is that treating the liver condition might help fix these brain problems, but more human studies are needed to confirm this works in people

The Research Details

Researchers used mice to study how fatty liver disease affects the brain. First, they fed some mice a special diet that caused them to develop fatty liver disease, similar to what happens in humans. Then they tested these mice on memory tasks and movement skills to see if their brains were affected. Next, the scientists used a new treatment called siRNA therapy that targets a specific protein in the liver called CNNM4. This treatment was designed to fix the liver problem without directly touching the brain. Finally, they tested the treated mice again to see if their brain function improved.

The researchers also looked inside the brains of the mice using advanced microscopy and genetic testing. They examined specific brain structures involved in memory (called the hippocampus) and counted different types of brain cells and connections between them. This allowed them to see exactly what was happening at the cellular level when the liver disease affected the brain.

This study design is important because it shows a direct connection between liver disease and brain problems. By treating only the liver and seeing brain improvements, the scientists proved that the liver disease is actually causing the brain issues, not just happening at the same time. This is a crucial finding because it means doctors might be able to help brain problems by treating the liver, rather than needing separate brain treatments.

This research was published in Science Advances, a highly respected scientific journal, which means it went through careful review by other experts. The study used controlled laboratory conditions with mice, which allows scientists to study the disease in a very precise way. However, because this was done in mice and not humans, we need to be cautious about assuming the same thing happens in people. The researchers did thorough testing of both behavior and brain structure, which strengthens their findings.

What the Results Show

Mice with fatty liver disease showed clear problems with memory and movement compared to healthy mice. Specifically, they had trouble remembering social interactions with other mice and had slower, less coordinated movements. When scientists looked at their brains, they found that the memory center (hippocampus) had fewer connections between brain cells and fewer new brain cells being created.

When the researchers treated the mice’s livers with the special siRNA therapy targeting CNNM4, something remarkable happened: the mice’s memory improved, their movement became more normal, and their brain cells started working better. The brain cells that had been damaged began to recover, and new brain cells started forming again. The treatment also fixed problems with the energy-producing parts of brain cells (mitochondria), which are crucial for brain function.

The improvements weren’t just in behavior—the scientists found that the actual structure and function of the brain had changed for the better. Brain cells that had lost their connections regrew those connections, and the genes responsible for creating new brain cells became active again.

Beyond the main findings, researchers discovered that the fatty liver disease reduced a specific type of brain cell called parvalbumin-positive interneurons, which are important for organizing brain activity. After treatment, these cells recovered. The study also showed that the liver disease affected how well the brain’s energy systems worked, and the treatment fixed these energy problems. Additionally, the research revealed that the liver disease reduced the growth of new brain cells in a specific brain region, but this process reversed with treatment.

Previous research suggested that fatty liver disease might be connected to brain problems, but scientists weren’t sure if the liver disease actually caused the brain issues or if they just happened together. This study is important because it proves the liver disease directly causes the brain problems. It also shows that the connection between liver and brain is stronger than previously thought, and that treating the liver can have major effects on brain function. This supports a growing area of research called the ’liver-brain axis’ that explores how liver health affects the brain.

This study was done in mice, not humans, so we can’t be completely sure the same results would happen in people. The researchers didn’t test the treatment in human patients, so we don’t know if it would be safe or effective in people yet. The study also didn’t look at how long the benefits last after treatment stops, or whether the treatment works for all types of fatty liver disease. Additionally, the mice were specifically bred for research and may not represent all people with fatty liver disease, since human genetics and lifestyles vary greatly.

The Bottom Line

If you have been diagnosed with fatty liver disease (MASLD), it’s important to work with your doctor on treatments to improve your liver health, as this research suggests it may also help protect your brain function. Current recommendations include losing weight if overweight, eating a healthy diet, exercising regularly, and limiting alcohol. While this specific siRNA treatment isn’t available for humans yet, the research suggests that future treatments targeting the liver could help prevent or reverse brain problems. Confidence level: This is promising early research, but we need human studies before making strong recommendations.

People with fatty liver disease or at risk for it (those who are overweight, have diabetes, or eat a high-fat diet) should pay attention to this research. People experiencing memory problems or cognitive issues should discuss with their doctor whether fatty liver disease might be a contributing factor. Healthcare providers treating liver disease should consider that their treatments might also be helping brain health. People with family histories of liver disease or cognitive problems may want to be extra careful about liver health. This research is less relevant for people with healthy livers and normal brain function.

In the mouse studies, improvements in brain function appeared within the timeframe of the treatment period, but we don’t know how quickly this would happen in humans. If a similar treatment becomes available for people, it might take weeks to months to see improvements in memory and thinking, similar to how other brain treatments work. Long-term benefits would need to be studied in human trials.

Want to Apply This Research?

  • Track liver health markers (if you have access to test results) such as liver enzyme levels and fat content, alongside cognitive function by noting any changes in memory, focus, or mental clarity in daily activities. Record these monthly to see if improvements in liver health correlate with better brain function.
  • Use the app to set and track goals for fatty liver disease management: maintain a healthy weight, follow a liver-friendly diet (low in processed foods and added sugars), exercise at least 150 minutes per week, and limit alcohol. These changes may help both your liver and brain health based on this research.
  • Create a long-term tracking system that monitors both liver health (through doctor visits and test results) and brain function (through self-reported memory, concentration, and mood). Set quarterly check-ins to review progress and adjust lifestyle changes as needed. Share results with your healthcare provider to ensure your treatment plan is working.

This research was conducted in mice and has not yet been tested in humans. The siRNA therapy described is not currently available as a treatment for people. If you have been diagnosed with fatty liver disease or are experiencing memory or cognitive problems, please consult with your healthcare provider before making any changes to your treatment plan. This article is for educational purposes only and should not be considered medical advice. Always discuss new research findings with your doctor to determine what’s appropriate for your individual situation.