Appetite-regulating hormone also shields liver from inflammation and scarring
McMaster University researchers found that the hormone GDF15 reduces liver inflammation and fibrosis even when body weight does not change. The hormone activates a brain-to-liver pathway that releases glucocorticoids, calming immune activity in the liver. This suggests new treatment approaches for advanced fatty liver disease.
The study employed mouse models engineered to closely replicate human MASH, integrating genetic, pharmacological, genomic, and spatial transcriptomics methods. Researchers traced GDF15's signal from the brain through the nervous system, triggering glucocorticoid release that suppressed liver inflammation and shifted immune cells into a protective state.
Crucially, these benefits appeared independent of food intake, body weight, or liver fat changes. The hormone also slowed fibrosis progression, challenging assumptions that GDF15's value stems solely from appetite suppression. This suggests the hormone may function as a natural defense mechanism against chronic liver injury, potentially complementing existing weight-loss therapies.
This discovery could reshape treatment approaches for millions affected by MASH, an advanced fatty liver condition that can progress to cirrhosis or liver failure. Since liver inflammation often persists even after significant weight loss, therapies targeting this newly identified brain-to-liver pathway may complement existing medications. Patients unable to achieve substantial weight reduction could particularly benefit, though human trials remain necessary to confirm whether these effects translate beyond mouse models.