McMaster University Research Reveals New Role for Hormone GDF15 in Liver Protection

Researchers at McMaster University have discovered that GDF15, a hormone previously recognized for its appetite-suppressing and weight-loss effects, also plays a crucial role in protecting the liver from inflammation through a newly identified signaling pathway. This finding, published in the journal Cell Metabolism on August 10, 2026, could lead to novel treatment strategies for advanced fatty liver disease.

The study demonstrated that GDF15 can significantly reduce liver inflammation and slow the progression of liver scarring, independent of any weight loss. This challenges the long-held perspective that the hormone’s benefits were largely associated with appetite regulation and body weight management.

A New Target for Advanced Fatty Liver Disease

Millions globally are affected by metabolic dysfunction-associated steatohepatitis (MASH), a severe type of fatty liver disease that can result in cirrhosis, liver cancer, and liver failure. While recent weight loss medications have enhanced the conditions for many patients, liver inflammation often persists even after substantial weight loss. The findings from McMaster’s research suggest that therapies targeting liver inflammation could be developed alongside existing fat-reduction treatments.

“Our findings show that GDF15 does much more than regulate appetite and body weight,” said Gregory Steinberg, a professor in McMaster’s Department of Medicine and co-director of the Centre for Metabolism, Obesity and Diabetes Research (MODR). “We discovered that GDF15 activates a natural brain-to-liver signaling pathway that helps suppress liver inflammation and reduce fibrosis, indicating it may be part of the body’s defense system against chronic liver injury.”

Mechanism of GDF15 in Liver Protection

Utilizing mouse models designed to closely mimic human MASH, the research team employed a combination of genetic, pharmacological, genomic, and spatial transcriptomics techniques to analyze GDF15’s impact. The results showed that GDF15 triggers signaling from the brain via the nervous system, leading to the release of glucocorticoids—steroid hormones essential for metabolism, immune function, and the body’s stress response.

These glucocorticoids appear to suppress liver inflammation without being influenced by changes in diet, body weight, or liver fat levels. Furthermore, GDF15 was found to slow the advancement of liver fibrosis as the disease progressed.

“GDF15 helps reprogram liver cells to reduce inflammation and scarring,” noted Dongdong Wang, the study’s first and corresponding author. “Instead of causing damage, GDF15 seems to calm the liver’s immune system, shifting immune cells into a more protective state and reducing inflammation.”

Implications for Future Therapies

In earlier research published in 2023, Steinberg and Wang illustrated that GDF15 assists in maintaining calorie burning during weight loss. The new findings present a contrasting function of the hormone: defending the liver through an unknown anti-inflammatory pathway. Together, these studies could influence the development of therapies specifically targeting liver inflammation, a significant contributor to MASH’s progression.

Steinberg, who is also an executive member of NexusHealth at McMaster and involved in preclinical research on potential drug candidates for liver disease, emphasized the need to integrate therapies that directly target inflammation with those that focus on body weight and fat reduction. “Understanding how the body naturally protects the liver may reveal new opportunities for more effective treatments for MASH patients,” he added.

The research involved contributions from collaborators Rune E. Kuhre and Sebastian B. Jørgensen of Novo Nordisk A/S and was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes of Health Research (CIHR), and Diabetes Canada. Novo Nordisk supported the research and supplied the GDF15 hormone used in the study.