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

GDF15 activates the GFRAL-HPA axis to suppress liver inflammation independently of weight loss in mouse models of MASH.

• Why it matters: Understanding whether GDF15 promotes or protects against liver injury is crucial for developing targeted therapies for metabolic liver diseases like MASH, where inflammation drives disease progression.
• What they did: Researchers used thermoneutral mouse models with genetic deletion and recombinant GDF15 treatment, measuring effects on liver inflammation, fibrosis, and immune cell profiles, while analyzing neuroendocrine signaling pathways.
• The result: GDF15 reduced liver inflammation and fibrosis independently of weight loss by activating the hypothalamic-pituitary-adrenal axis, increasing corticosterone and glucocorticoid receptor signaling, and remodeling immune cell populations.