Newswise — Rockville, Md. (July 16, 2025)—Aerobic exercise and a high capacity for exercise may protect against metabolic dysfunction-associated steatotic liver disease (MASLD), also known as fatty liver disease, by increasing the conversion of cholesterol into bile acids, according to a new study published in Function. The paper has been selected as an APSselect article for July by the American Physiological Society (APS). 

MASLD is a chronic condition in which excessive fat is stored in the liver. It is tied to high cholesterol, Type 2 diabetes, obesity and insulin resistance. It can also lead to liver disease and increases the risk of heart disease.

While exercise is known to prevent and treat fatty liver, researchers don’t yet understand exactly how this happens.

This new study offers insights: Researchers propose that exercise prevents or reduces fatty liver, in part, by improving bile acid metabolism. The most prominent way cholesterol is removed from the body is by its conversion to bile acids, which aid the digestion of fat and trigger signals that improve how the body uses sugar and fat. By stimulating bile acid metabolism, exercise increases the disposal of cholesterol and activates signals that improve how the body processes food.

In the study, rats bred to have genetically high- or low-exercise capacity were provided a high-fat diet, which normally causes fatty liver. This design was chosen because exercise capacity has been independently linked to lower risk for fatty liver disease in people. In addition, genetically identical mice were fed a high-fat diet, and half were allowed access to voluntary running wheels to simulate daily exercise in humans. A separate group of mice that lacked the ability to make bile acids were studied to test whether bile acid metabolism is necessary for the protective effects of exercise.

Key findings included:

• High-exercise capacity rats had higher liver bile acid production, more bile acids in their feces, and lower blood levels of bile acids compared to the low-exercise capacity group.

• Daily exercise also increased bile acid synthesis, fecal bile acid loss and protected against fatty liver in the genetically identical mice. This demonstrates that daily exercise provides the same benefit as high exercise capacity due to genetic differences.

• Mice with an impaired ability to produce bile acids experienced no benefit of exercise in preventing fatty liver.

• Aerobic exercise increased bile acid production, and this process was required to prevent fatty liver.

“Importantly, our results identify bile acid synthesis as a key mediator between aerobic capacity, exercise and hepatic energy metabolism that may also be linked to whole-body metabolism and long-term risk for Type 2 diabetes and MASLD,” the researchers wrote. “[B]ile acid synthesis plays a critical role in aerobic capacity and exercise ability in combating MASLD.” [News Wise/VP]