GDF15 Activates Brain-to-Liver Anti-Inflammatory Pathway
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- McMaster University researchers discovered GDF15 activates a brain-to-liver signaling pathway that triggers glucocorticoid release, suppressing liver inflammation in mouse models engineered to mimic human MASH.
- The protective effects—reduced inflammation and slowed fibrosis—occurred regardless of changes in food intake, body weight, or liver fat, challenging the long-held view that GDF15's benefits stem primarily from appetite and weight regulation.
- Published in Cell Metabolism on August 10, 2026, the study combined genetic, pharmacological, genomic, and spatial transcriptomics techniques to trace how GDF15 reprograms liver immune cells into a "more protective and less active state."
- Gregory Steinberg (senior author, co-director of McMaster's Centre for Metabolism, Obesity and Diabetes Research) and first/corresponding author Dongdong Wang led the research, which specifically examined fibrosis—the scarring that drives MASH progression toward cirrhosis, liver cancer, and liver failure.
- A 2023 study by the same team showed GDF15 helps maintain calorie burning during weight loss; the new findings reveal a distinct second function—anti-inflammatory liver protection—through neuroendocrine glucocorticoid signaling.
- The study included collaborators Rune E. Kuhre and Sebastian B. Jørgensen of Novo Nordisk, with funding from NSERC, CIHR, and Diabetes Canada; Steinberg is also co-founder and CSO of Espervita Therapeutics, which is developing a separate drug candidate for advanced liver disease.
Why it matters: Millions of people live with MASH, an advanced fatty liver disease that can progress to cirrhosis, liver cancer, or liver failure—and inflammation often persists even after substantial weight loss. The discovery of a direct brain-to-liver anti-inflammatory pathway offers a potential therapeutic target that works independently of weight or fat reduction, complementing existing approaches that focus on metabolism and appetite.
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