New University of Minnesota research sheds light on fighting liver disease, offering new ideas for better treatments

MINNEAPOLIS/ST. PAUL (05/14/2025) — New research from the University of Minnesota Medical School reveals how the liver may try to protect itself from serious liver damage, called a metabolic dysfunction-associated steatotic liver disease (MASLD). The condition affects over a third of U.S. adults and is expected to impact 122 million Americans by 2050, and is a leading cause of cirrhosis and the requirement for liver transplant. 

Published in The Journal of Clinical Investigation, the study found that in humans, a liver process called ketogenesis — the body’s way of breaking down fat — may actually help fight off severe liver damage. In a related study from the research team, published in Science Advances, they found that ketone bodies — substances made by your liver when it breaks down fat for energy — may also play a role in supporting the production of healthy fats that optimize the function of cells within our organs.

"These studies show unexpected connectivity between the nutrients we eat and the products of our body's own metabolism,” said Patrycja Puchalska, Ph.D., an assistant professor at the University of Minnesota Medical School and co-lead researcher on both studies. “Our newest data suggest that this connection might not be limited to the liver — it could also potentially influence brain development in newborns."

The study used preclinical models that were genetically unable to make ketones and got sicker when fed a high fat diet. However, when ketogenesis was active, the fat burned off efficiently and the liver built healthy fats called polyunsaturated fatty acids (PUFAs). These healthy fats are known to protect the liver from damage and are commonly found in fish oils. 

"Our findings suggest that interventions that stimulate ketone body production, such as low-carbohydrate diets and intermittent fasting, should be considered for treating MASLD," said Eric Queathem, a graduate student at the University of Minnesota Medical School.

This new understanding could open the door for more targeted treatments. Rather than just focusing on burning fat, future therapies could support or mimic ketogenesis to help counter the progression of liver disease.

“These studies provide quantifiable biomarkers of our healthy feeding and fasting cycles, which should allow us to predict, at a personalized level, when our feeding and fasting patterns are optimizing our health, and when they are not,”  according to Peter A. Crawford, MD, Ph.D., a professor at the University of Minnesota Medical School and co-lead author of the two studies. 

Funding was provided by NIH grants DK091538, DK122832, HL166142, DK136772 and AG069781.