Growth differentiation factor 15
Growth differentiation factor 15 (GDF15), also known as growth/differentiation factor-15, is a secreted, stress-inducible cytokine of the transforming growth factor-β superfamily.
Growth differentiation factor 15 (GDF15), also known as growth/differentiation factor-15, is a secreted, stress-inducible cytokine of the transforming growth factor-β superfamily. It has emerged as a systemic signal associated with metabolic dysfunction, inflammation, neuroimmune processes, and cardio-renal disease. Circulating GDF15 has been investigated as a biomarker in conditions including obesity, type 2 diabetes, metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, diabetic kidney disease, heart failure, dementia, and all-cause mortality.
Current research is also examining GDF15 as a therapeutic target rather than solely as a biomarker. Its clinical and experimental context includes metformin-associated changes in circulating GDF15, relationships with body weight and weight loss, and possible interactions with pathways involving adipose tissue, cellular senescence, and the GDF15 receptor GFRAL. Engineered delivery systems, including CircRNA-GDF15@LNP, are being developed to provide sustained GDF15 protein expression, while other studies are assessing whether GDF15-related signaling influences liver inflammation, neuroimmune function, HIV reservoir markers, and mental-health outcomes.
Rebuilt from PubMed 18 Sept 2026 · no new papers today
Where the papers sit
9 papers study growth differentiation factor 15 directly. Those 9 are one subject: Systemic GDF15 Biology. GDF15 is being studied as a systemic regulator linking obesity, steatohepatitis, diabetes, kidney and cardiovascular disease with neuroimmune and mood outcomes. Human associations and engineered GDF15 therapy suggest biomarker and metabolic-treatment potential, but mechanisms and clinical direction remain unsettled. No way of splitting those 9 scores better than chance. 1 new direction follows.
GDF15 is a weight-loss-independent suppressor of MASH inflammation and fibrosis
The thermoneutral mouse models of MASH studied by the GDF15/GFRAL deletion and recombinant-protein experiments 42575092Aug depart from treating GDF15 primarily as a metabolic-stress marker or weight-loss mediator: deleting GDF15 or GFRAL worsened hepatic inflammation and fibrosis without changing steatosis or insulin resistance, whereas recombinant GDF15 improved liver injury more than matched caloric restriction despite identical weight loss. This assigns GDF15 a distinct hepatoprotective role, mediated through GFRAL-dependent hypothalamic-pituitary-adrenal and hepatic glucocorticoid signaling that remodels the immune-fibrotic niche, and shifts the therapeutic rationale from reducing weight or steatosis to directly resolving liver inflammation and fibrosis.
Recent Findings on Growth differentiation factor 15
GDF15 Across Human Disease: Circulating GDF15 rises with cardiometabolic risk and biopsy-proven MASH and liver fibrosis, but it distinguishes obese from control participants better than adjacent risk groups 42747598Sep42489816Jul. In thermoneutral mouse models, GDF15-GFRAL-HPA signaling suppresses hepatic inflammation and fibrosis independently of weight loss, while diabetic kidney and cardiovascular disease studies describe protective acute effects but potentially maladaptive chronic signaling 42575092Aug42149139May. Engineered CircRNA-GDF15@LNP promotes sustained weight loss and metabolic regulation through PPARα/γ signaling and UCP1 expression, while metformin increases glycolysis and GDF15 but not FGF21 in humans 42323019Jun41928890Apr. Midlife plasma GDF15 predicts later dementia, particularly vascular dementia, and alters neuroimmune pathways, whereas its association with depressive symptoms reverses with age and shows no association with anxiety 42361163Jun42025637Apr. ART-treated people with HIV show monocyte-derived GDF15 elevations that correlate with integrated HIV DNA and soluble urokinase plasminogen activator receptor but with few inflammatory markers, reinforcing GDF15’s emerging use in risk stratification and mechanistic studies 41966981Apr.
Written from 9 PubMed abstracts, each one cited by PMID above. Published: 2026-09-11. Last written: 2026-09-18 by GPT. Drafted by language models from published abstracts; not medical advice.