Weight-loss hormone found to protect liver even without weight loss
GDF15 hormone reduces liver inflammation and slows fibrosis progression, study reveals.
1Unexpected effect of the hormone
Researchers at McMaster University discovered that GDF15, a hormone known for reducing appetite and aiding weight loss, also protects the liver from inflammation. Published in Cell Metabolism on August 10, 2026, the study showed that the hormone reduces liver inflammation and slows fibrosis progression even without weight loss. This finding challenges the view that the hormone's benefits are limited to appetite and body weight regulation.
2Hope for MASH disease
Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of fatty liver disease affecting millions worldwide, potentially leading to cirrhosis, liver cancer, and failure. While new weight-loss drugs have improved outcomes for many patients, liver inflammation often persists even after significant weight loss. This study identifies a biological pathway that directly regulates inflammation, paving the way for new treatment options.
3Brain-liver signaling pathway
Researchers examined how GDF15 affects mouse models mimicking human MASH. Using genetic, pharmacological, and genomic techniques, they found that the hormone initiates signaling from the brain through the nervous system, triggering glucocorticoid release. These steroid hormones play critical roles in metabolism, immune activity, and the body's stress response.
4Effect independent of food intake
The study's most striking finding was that GDF15's protective effects occur independently of changes in food consumption, body weight, or liver fat. The hormone also slows the progression of fibrosis, the accumulation of scar tissue that occurs as liver disease advances. This suggests the hormone calms the immune system rather than causing liver damage.
5Reprogramming immune cells
Co-author Dongdong Wang noted that GDF15 reprograms liver cells using advanced spatial technology to reduce inflammation and scarring. The hormone shifts immune cells into a more protective, less active state, preventing liver damage. This mechanism may be part of the body's natural defense system against chronic liver injury.
6Connection to 2023 findings
Steinberg and Wang's 2023 research showed GDF15 helps maintain calorie burning during weight loss. The new study reveals the same hormone protects the liver through a previously unknown anti-inflammatory pathway. Together, these studies could guide the development of new therapies targeting liver inflammation, a major driver of MASH progression.
7Complementary approach to current treatments
Steinberg emphasized that current therapies mainly focus on reducing body weight and liver fat, but this study suggests combining them with therapies directly targeting inflammation could be valuable. Understanding how the body naturally protects the liver may lead to more effective treatments for MASH patients.
8Funding and collaborations
The study was funded by Canada's Natural Sciences and Engineering Research Council (NSERC), Canadian Institutes of Health Research (CIHR), and Diabetes Canada. Novo Nordisk A/S researchers Rune E. Kuhre and Sebastian B. Jørgensen contributed to the study. The company also provided the GDF15 hormone used in the research and supported the project.