Growth Differentiation Factor 15 (GDF15) is a stress-responsive protein. It is widely used as a biomarker for various disease states and is increasingly recognized as a key player in regulating metabolism, inflammation, and cellular responses to stress.
Metabolic regulation: GDF15 can reduce food intake and body mass by binding to its receptor, GFRAL (GDNF Family Receptor Alpha-Like), in the hindbrain. This makes the GDF15-GFRAL pathway a target for treating obesity and metabolic disorders.
Appetite suppression: GDF15's ability to suppress appetite is significant in both metabolic diseases and conditions like cancer cachexia, where it contributes to weight loss. Role in disease Because GDF15 levels are elevated in many pathological states, it serves as a valuable biomarker for disease severity and prognosis.
Cardiovascular disease: Elevated GDF15 levels are strongly associated with heart failure, coronary artery disease, and other cardiac events. It is a prognostic biomarker for adverse cardiovascular outcomes.
Cancer cachexia: This metabolic wasting disorder is associated with high GDF15 levels, which drive appetite loss. Therapeutics aimed at inhibiting GDF15 show promise in treating this condition.
Mitochondrial diseases: Elevated GDF15 is a marker for various mitochondrial disorders, indicating the need for further diagnostic investigation.
Metabolic disorders: Higher GDF15 levels are seen in individuals with obesity and type 2 diabetes. It is a potential biomarker for insulin resistance and future diabetes risk.
Citations:
- Yang L, et al. GFRAL is the receptor for GDF15 and is required for the anti-obesity effects ofthe ligand. Nat Med. 2017 Aug 28. doi: 10.1038/nm.4394.
- Nandini Nair, and Enrique Gongora "Correlations of GDF-15 with sST2, MMPs, and worsening functional capacity in idiopathic dilated cardiomyopathy: Can we gain new insights into the pathophysiology?" J Circ Biomark. 2018 Jan 19;7:1849454417751735. doi: 10.1177/184945441775173
- Jörg Wischhusen, Ignacio Melero, Wolf Fridman. Growth/Differentiation Factor-15 (GDF-15): From
Biomarker to Novel Targetable Immune Checkpoint. Frontiers in Immunology, Frontiers, 2020, 11,
pp.951. ff10.3389/fimmu.2020.00951ff. ffhal-02878344f
