The Role of FGF21 Hormone in Reversing Fatty Liver Disease

Recent advancements in liver disease research highlight the promising potential of the hormone FGF21 (fibroblast growth factor 21) in combating fatty liver conditions, specifically MASLD (metabolic dysfunction-associated steatotic liver disease) and its progression to MASH (metabolic dysfunction-associated steatohepatitis). A comprehensive study published in Cell Metabolism by researchers at the University of Oklahoma reveals how FGF21 can effectively reverse liver fat accumulation and fibrosis in mouse models.

Fatty liver disease involves excessive fat buildup in the liver, which can lead to dangerous complications such as fibrosis and cirrhosis. Currently, only one FDA-approved treatment exists for advanced stages of the disease, underscoring the need for new therapeutic strategies.

The study’s lead author, Dr. Matthew Potthoff, emphasizes that FGF21 acts primarily by signaling the brain to influence liver function. This hormone initiates a feedback loop: it sends a message to the brain, which then adjusts nerve activity to protect and regulate the liver. This indirect signaling is responsible for the significant reduction in liver fat and fibrosis observed in the study, alongside lowering cholesterol levels.

Interestingly, FGF21 functions similarly to GLP-1, a hormone that influences appetite and blood sugar control. Both hormones originate from peripheral tissues—GLP-1 from the intestine and FGF21 from the liver—and primarily communicate with the brain to regulate metabolism.

The research demonstrates that administration of FGF21 during ongoing calorie-rich diets can lead to substantial metabolic improvements. Not only does it decrease stored fat, but it also reverses the pathological fibrosis that characterizes advanced liver disease. These findings suggest that therapies based on FGF21 signaling may be highly effective for treating fatty liver disease and preventing its progression.

With multiple drugs targeting FGF21 currently in late-stage clinical trials, understanding its mechanism of action paves the way for innovative treatments. Future therapies might leverage this pathway to provide targeted, effective solutions for patients suffering from this widespread disease.

Source: https://medicalxpress.com/news/2025-05-hormone-fgf21-reverse-fatty-liver.html