Connection between liver and brain in the context of metabolic liver disease revealed

Medical Xpress / University of Seville / Science Advances ^ | Oct. 30, 2025 | Teresa Cardoso Delgado et al

[ConservativeMind]

A multidisciplinary research team has discovered that liver alterations associated with metabolic dysfunction–associated fatty liver disease (MASLD) can directly cause cognitive and neurological impairments, and that these effects can be reversed by a therapy exclusively targeting the liver. The findings establish the existence of a "liver–brain axis" that is not only clinically relevant but also therapeutically actionable.

The study demonstrates that animal models of diet-induced metabolic liver disease show alterations in social memory and sensory processing, accompanied by dysfunctions in the hippocampus, a key region for memory and learning.

Most promisingly, these alterations were reversed by treating the liver with an innovative siRNA-based therapy targeting CNNM4, a magnesium transporter altered in this hepatic condition, using a highly specific GalNAc-siRNA delivery system.

"Our work demonstrates that fatty liver and hepatic inflammation can directly affect the brain and behavior. This opens up an entirely new therapeutic avenue: treating the liver to improve cognitive function," explains Martínez-Chantar.

"Moreover, we show how cutting-edge molecular biology technologies and targeted therapies can have a real impact on brain function, combining precision and efficacy," adds Cardoso Delgado.

[ConservativeMind]

Cognitive and neurological functions can improve by getting rid of one’s fatty liver.

Reducing weight and taking 300 mg of pantethine twice a day can both help do this.

[ConservativeMind]

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[telescope115]

Interesting. My situation was a little different; I had Primary Sclerosing Cholangitis, which caused cirrhosis. I retired early not only because of the physical symptoms of the disease, but I was becoming less confident in my ability to set up and operate machinery safely- I could tell I wasn’t as sharp as I used to be. I made the decision to retire before I either wrecked something or hurt myself, or both.
Now, 4+ years later after the transplant, I believe my mind is in better shape than it was then. I have always believed that my brain was affected by my failing liver.