This Weight-Loss Hormone May Protect the Liver Even Without Weight Loss

Researchers at McMaster University have uncovered an unexpected role for GDF15, a naturally occurring hormone already known for reducing appetite and supporting weight loss. A study published in the journal Cell Metabolism on August 10, 2026, found that GDF15 can reduce liver inflammation and slow the development of liver scarring even when weight loss does not occur — challenging the long-held view that the hormone's benefits are tied primarily to its effects on appetite and body weight.

Millions of people worldwide are affected by metabolic dysfunction-associated steatohepatitis (MASH), an advanced form of fatty liver disease that can eventually lead to cirrhosis, liver cancer and liver failure. New weight-loss medications have improved outcomes for many patients, but liver inflammation can remain even after substantial weight loss. "Our findings show that GDF15 does much more than regulate appetite and body weight," said Gregory Steinberg, professor in McMaster University's Department of Medicine and co-director of the Centre for Metabolism, Obesity and Diabetes Research. "We discovered that GDF15 activates a natural brain-to-liver signaling pathway that helps suppress liver inflammation and reduce fibrosis."

To explore how GDF15 affects advanced liver disease, the team used mouse models designed to closely reproduce human MASH, combining genetic, pharmacological, genomic and spatial transcriptomics techniques. They found that GDF15 initiates signaling from the brain through the nervous system, ultimately causing the release of glucocorticoids — steroid hormones important for metabolism, immune activity and the body's response to stress — which then help suppress inflammation in the liver. Researchers observed these protective effects regardless of changes in food consumption, body weight or liver fat, and GDF15 also appeared to slow the progression of liver fibrosis, the buildup of scar tissue as liver disease advances.

"Instead of causing liver damage, GDF15 appears to help calm the liver's immune system. It shifts immune cells into a more protective and less active state," said Dongdong Wang, first and corresponding author of the study and assistant professor in McMaster's Department of Medicine.

Research published in 2023 by Steinberg and Wang had shown that GDF15 helps the body maintain calorie burning during weight loss; the new findings reveal a separate, previously unknown anti-inflammatory pathway for the same hormone. The study also included collaborators Rune E. Kuhre and Sebastian B. Jørgensen of Novo Nordisk A/S, which supplied the GDF15 hormone used in the research, and was funded by Canada's Natural Sciences and Engineering Research Council, the Canadian Institutes of Health Research and Diabetes Canada.