The Surprising Discovery That May Change Fatty Liver Treatment

Is it possible to protect the liver even without losing weight? A new study published on August 10 in the scientific journal Cell Metabolism points to a surprising mechanism that may change the way researchers look at the treatment of advanced fatty liver disease. The researchers found that the hormone GDF15 may activate a communication pathway between the brain and the liver, which helps reduce inflammation and slow down the scarring process in the liver — in a way that is independent of weight loss.

The study, led by researchers from McMaster University in Canada and in collaboration with researchers from Novo Nordisk, focused on GDF15 — a natural hormone produced in the body and known, among other things, for its ability to influence appetite centers in the brain and reduce food intake. However, the new findings suggest that its role may be broader than previously thought.

Not just weight loss

Metabolic dysfunction-associated steatotic liver disease, now known as MASLD, can progress in some patients to MASH — a condition in which, alongside fat accumulation, inflammation and liver damage also develop. Over time, fibrosis may develop, meaning scarring of the liver tissue, and in advanced cases, the disease can progress to cirrhosis, liver failure, and even liver cancer. One of the key factors in treating the disease is weight reduction and improvement of the metabolic state. However, even when significant weight loss occurs, the inflammation in the liver does not necessarily disappear completely. This is where the new mechanism identified by the researchers comes into play. Using mouse models that simulate human MASH, alongside genetic, pharmacological, genomic, and advanced spatial transcriptomics technologies, the researchers examined how GDF15 affects the disease.

The message sent from the brain to the liver

The researchers found that GDF15 activates signaling in the brain that leads, through the nervous system, to the release of glucocorticoids — natural steroid hormones involved, among other things, in the regulation of the immune system, metabolism, and the body's response to stress. The glucocorticoids helped suppress the inflammatory response in the liver. Surprisingly, this effect was observed independently of changes in food intake, body weight, or the amount of fat in the liver. In addition, the researchers found that GDF15 helped limit the progression of fibrosis — the accumulation of scar tissue that characterizes advanced liver disease. Analysis of liver cells also indicated a change in the behavior of immune system cells toward a less inflammatory and more protective state.

A new direction for treatment?

The potential significance of the findings is that in the future, treatment for advanced fatty liver disease may not focus only on weight loss and reducing the amount of fat in the liver, but also on biological pathways that more directly suppress inflammation and the scarring process. The researchers note that understanding the body's natural defense mechanism may help in the development of new treatments that will complement metabolic therapies and weight loss drugs.

However, the road from experimental treatment to patient treatment is still long. The current study was conducted in mouse models and did not prove that administering GDF15 can treat MASH in humans. Further studies, and eventually clinical trials, will be needed to determine whether the mechanism found can be translated into safe and effective treatment for humans. Despite this caveat, the finding provides a glimpse into a biological pathway that was not previously known: a hormone that communicates with the brain may activate a protective mechanism for the liver from it — and reduce damage even without weight loss.