GDF15 suppresses liver inflammation independently of weight loss through neuroendocrine glucocorticoid signaling.

GDF15 reduces liver inflammation and fibrosis independently of weight loss by activating neuroendocrine glucocorticoid signaling via GFRAL.

• Why it matters: Understanding whether GDF15 promotes or protects against liver injury is crucial for developing targeted therapies for metabolic liver diseases like MASH, which lack effective treatments.
• What they did: Researchers used thermoneutral mouse models with genetic deletion and recombinant GDF15 administration, observing effects on liver inflammation, fibrosis, and immune cell profiles, focusing on GFRAL and HPA axis pathways.
• The result: GDF15’s activation of the GFRAL-HPA axis increased corticosterone levels, remodeled immune cell populations, and suppressed inflammation, revealing a weight-loss-independent mechanism to protect the liver.