UCLA Researchers Find a New Approach to Treating Fatty Liver Disease

Hepatic steatosis, or fatty liver disease, can be prevented or slowed down by chemically modifying certain RNA molecules. Livers

Gene therapy may protect against Hepatic steatosis, better known as “fatty liver disease.” This is the conclusion of a study conducted by researchers at the University of California Los Angeles and published July 19 in the journal Nature Metabolism. This work in mice showed that a chemical change in certain RNA molecules, which carry genetic instructions in the DNA for the production of cellular proteins, can protect against the accumulation of fat in the liver. The accumulation of fat in the liver can lead to advanced liver conditions such as cirrhosis and cancer.

Hepatic steatosis occurs as a result of dietary or genetic factors and, just like alcohol abuse, can lead to cirrhosis. Elevated levels of fat in the liver may be associated with a high risk of cardiovascular disease.

Previous studies have shown that RNA molecules can undergo chemical changes with positive or negative consequences.

Restricting fat accumulation in the liver

To gain insight, the researchers used a mouse model in which a mouse carrying the RNA modification N⁶-methyladenosine (m⁶A) was compared with a mouse without the mutation. And they analyzed the effect of different levels of dietary fat contents to assess the effect of this modification on hepatic steatosis. At the same time, they used measurements from people who had undergone liver biopsies (in particular, bariatric surgery) to correlate markers of m6A modification with liver fat content. They found that m⁶A appears to act as a protective checkpoint that slows fat accumulation in the liver. Hence the idea of developing treatments for fatty liver disease using these chemical modifications to prevent or slow liver disease.

The m⁶A modification, which has been identified as a component of fatty liver disease, also appears to be differentially expressed in females and males in mouse models, which would explain why females tend to have higher levels of fatty liver.