SUN-819 Growth Differentiation Factor 15 in Health and Diseases

Abstract Disclosure: H.M. Heshmati: None. H.S. Abu-Lebdeh: None. Background: Growth differentiation factor 15 (GDF15) is a peptide hormone produced by the placenta during pregnancy and by several other organs (e.g., prostate, bladder, kidney, pancreas, and endometrium). It is a member of the transforming growth factor-β superfamily. The gene encoding for GDF15 is located on chromosome 19. The mature GDF15 has 112 amino acids and binds to glial cell-derived neurotrophic factor family receptor alpha-like. GDF15 is involved in the maintenance of homeostasis and contributes to the pathogenesis of several medical conditions. This literature analysis provides an update on the relevance of GDF15 in health and few selected diseases. Methods: A systematic search of literature was conducted using the search terms growth differentiation factor 15, pregnancy, heart failure, anorexia, obesity, diabetes, and cancer. Results: In control subjects, the median serum GDF15 level is around 680 pg/mL and increases with aging. There is an increase in GDF15 secretion during pregnancy (third trimester serum levels > 20,000 pg/mL) and under other stressful conditions such as inflammation, myocardial ischemia, pulmonary diseases, diabetes, and cancer. GDF15 is involved in the maintenance of cell and tissue homeostasis. It has anti-inflammatory, immunomodulatory, and anorectic properties. The high serum GDF15 levels observed during pregnancy plays an important role in the feto-maternal immunotolerance. Low serum GDF15 levels have been reported in pregnancies with complications (e.g., preeclampsia and miscarriage). Serum GDF15 levels are negatively correlated with body mass index. Treatment with metformin in patients with or without type 2 diabetes stimulates GDF15 production, and this can explain, at least in part, the weight-loss property of metformin. In patients with heart failure or cancer, the increased serum GDF15 levels contribute to cachexia (anorexia and weight loss). Serum GDF15 level has the potential to be used as a biomarker for disease diagnosis and prognosis (e.g., biomarker for heart failure and pancreatic cancer). High serum GDF15 levels are associated with poor prognosis and predict all-cause mortality. Based on the GDF15 properties related to appetite and body weight control, GDF15 analogs and antagonists can be considered in the weight management of various conditions such as obesity (induction of anorexia with GDF15 analogs), and heart failure or cancer (reduction of cachexia with GDF15 antagonists). Conclusion: GDF15, a hormone synthesized by several organs including placenta, prostate, bladder, kidney, pancreas, and endometrium, has an important role in multiple physiological and pathological conditions. Its serum level can be considered as a biomarker for the diagnosis and prognosis of several diseases. GDF15 analogs and antagonists have the potential to be used in the weight management of obesity and cardiac or cancer cachexia. Presentation: Sunday, July 13, 2025