Scientists at Yale University have made a discovery that could lead to better treatment for people at risk of fatty liver disease.
Their new study, published in Cellular and Molecular Gastroenterology and Hepatology, shows that blocking certain hormones may help stop fat from building up in the liver—especially in people with a high-risk gene.
Fatty liver disease happens when too much fat collects in the liver.
This can cause serious problems, like liver damage, scarring, or even liver cancer. In some cases, people with severe fatty liver disease may need a liver transplant.
Today, around 30% of people worldwide have fatty liver disease that isn’t caused by alcohol—and that number is growing due to rising rates of obesity and type 2 diabetes.
One gene variant in particular—called PNPLA3I148M—greatly increases the risk of developing a type of fatty liver disease known as MASLD (Metabolic Associated Steatotic Liver Disease). But scientists still don’t fully understand how this gene causes fat to build up in the liver.
To find answers, researchers at Yale used mice that had the same risky gene. When these mice were fed a high-sugar diet, they stored less fat in normal body fat tissues (like belly fat) and more fat in their livers, compared to mice without the gene.
This pointed to a problem with how their body handled fat outside of the liver.
“This suggested to us that something might be going wrong in the body’s normal fat storage process,” said Dr. Daniel Vatner, lead researcher and assistant professor of medicine at Yale.
The researchers then looked at a group of hormones called catecholamines (like adrenaline), which help control how fat is stored and used in the body.
When the genetically modified mice were given a drug that mimicked these hormones, they broke down more fat from their body fat stores. But instead of being burned off, the fat moved into the liver.
To stop this process, scientists gave the mice beta blockers—common drugs used to treat heart conditions. These drugs block hormone signals like adrenaline. The mice that took beta blockers had less fat buildup in their livers, showing that the treatment might help prevent fatty liver disease in people with the high-risk gene.
This research is still in early stages, and more work is needed to see if the findings apply to humans. But Dr. Vatner hopes this could lead to new treatments in the future. “In 10 years, we may be using this science to help people with fatty liver disease,” he said.
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