The liver may have an unexpected ally in the brain.
Scientists at McMaster University have found that a hormone called GDF15 can start a chain of signals in the brain that ultimately helps calm inflammation and reduce scarring in a badly damaged liver.
GDF15 has attracted attention because it can suppress appetite and contribute to weight loss. Until now, many of its health effects were thought to come mainly from people or animals eating less and becoming leaner.
The new research shows that the story is more complicated. GDF15 appears to protect the liver through a separate brain-to-liver communication system, and the protection can occur without changes in body weight, food intake or liver fat.
The study was published in Cell Metabolism on August 10, 2026. It was carried out by a McMaster University team led by researchers including Gregory Steinberg and Dongdong Wang.
The scientists were studying metabolic dysfunction-associated steatohepatitis, commonly shortened to MASH. It is an advanced form of fatty liver disease in which fat accumulation is joined by inflammation and damage to liver cells.
Fatty liver disease has become increasingly common alongside obesity and type 2 diabetes. Early disease may cause few symptoms, which means people can have liver damage for years without realizing it.
MASH is more dangerous because continuing inflammation can trigger fibrosis, the body’s attempt to repair injury by laying down scar tissue. If that process continues, severe fibrosis can develop into cirrhosis and greatly increase the risk of liver failure and liver cancer.
Weight loss can be extremely helpful because it reduces many of the metabolic pressures that contribute to fatty liver disease. New weight-loss medicines have therefore created important treatment opportunities for people with obesity and related liver problems.
Yet doctors face an important problem. Some patients can lose substantial weight and liver fat while still having inflammation, meaning one of the major forces behind future liver damage remains active.
The McMaster researchers wanted to understand whether GDF15 might influence this inflammation directly. They studied mice that develop liver changes designed to resemble advanced human MASH and used detailed methods to map what was happening in different cells.
The experiments revealed a surprising route. GDF15 signaled to the brain, and the brain then communicated through the nervous system in a way that increased the release of the body’s own glucocorticoid hormones.
Glucocorticoids are steroid hormones produced naturally by the adrenal glands. They help control stress, metabolism and immune activity and are related to medicines doctors use to reduce inflammation in many diseases.
In the study, these naturally released hormones helped turn down inflammation in the liver. The effect did not depend on the animals losing weight or eating less, showing that GDF15 was doing more than controlling appetite.
The researchers also saw changes in the liver’s immune cells. Instead of remaining highly active and promoting inflammation, some cells moved toward a quieter state that appeared to be less damaging.
This calming effect was accompanied by less progression of liver fibrosis. Because fibrosis is closely linked to serious long-term outcomes in MASH, finding ways to slow scar formation is a major goal of liver research.
First and corresponding author Dongdong Wang said the hormone appears to reprogram liver cells in ways that reduce inflammation and scarring. Senior author Gregory Steinberg described the pathway as evidence that GDF15 may form part of the body’s natural defense against chronic liver injury.
The discovery adds to earlier work by the same researchers. In 2023, they reported that GDF15 helps maintain the body’s energy use during weight loss, while the latest study identifies an entirely different protective action involving liver inflammation.
This creates an interesting treatment idea. Instead of relying only on medicines that help patients lose weight and reduce liver fat, future therapies might combine those benefits with a second approach that directly switches down harmful inflammation.
The study is scientifically strong because the researchers used several different experimental methods and examined the liver at a detailed cellular level. But its biggest limitation is equally important: results from mice do not always predict what will happen in humans.
Scientists must now determine whether the same pathway operates in people with MASH and whether it can be targeted safely. Glucocorticoids have powerful effects throughout the body, so any treatment based on this pathway would need to avoid disrupting normal hormone and immune functions.
The findings therefore represent a new direction rather than a ready-to-use therapy. Still, discovering that the brain can send a natural anti-inflammatory message to a diseased liver could help researchers design treatments that address a stubborn part of MASH that weight loss alone may not solve.
If you care about health, please read studies that herbal supplements could harm your heart rhythm, and how eating eggs can help reduce heart disease risk.
For more health information, please see recent studies that apple juice could benefit your heart health, and results showing yogurt may help lower the death risks in heart disease.
Source: McMaster University
