Endocrine Abstracts

JOINT545

Introduction: Growth differentiation factor 15 (GDF15), a peptide hormone produced by the placenta during pregnancy but also by several other organs (e.g., prostate, bladder, kidney, pancreas, and endometrium), is a member of the transforming growth factor-β superfamily. The gene of 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 plays an important role in several pathological conditions (e.g., cardiovascular diseases, autoimmunity, obesity, diabetes, and cancer). This review presents an update on the relevance of GDF15 in weight management in patients with obesity, heart failure, and cancer.

Methods: A systematic search of literature was conducted using the search terms growth differentiation factor 15, pregnancy, heart failure, autoimmunity, anorexia, obesity, diabetes, cancer, and weight management.

Results: The median serum GDF15 level in control subjects is around 680 pg/ml and increases with aging. There is an increase in GDF15 secretion under stressful conditions (e.g., pregnancy, inflammation, myocardial ischemia, pulmonary diseases, diabetes, and cancer). GDF15 plays an important role in the maintenance of cell and tissue homeostasis. It has anti-inflammatory and immunomodulatory properties. GDF15 regulates appetite and body weight by inducing anorexia which results in reduction of food intake. In a study of non-obese monozygotic twin pairs, serum GDF15 levels were negatively correlated with body mass index (BMI) within twin pairs, meaning that subjects with lower serum GDF15 levels had a higher BMI than their corresponding twin. In metformin-treated patients with or without type 2 diabetes, metformin stimulates GDF15 production, contributing to the weight-loss property of metformin. The increased serum GDF15 levels in patients with heart failure or cancer contribute to cachexia (anorexia and weight loss). In view of the above GDF15 properties, GDF15 analogs and antagonists can be used in the weight management of obesity (reduction of body weight by inducing anorexia using GDF15 analogs) and heart failure or cancer (reduction of cachexia by improving appetite and increasing body weight using GDF15 antagonists).

Conclusion: GDF15, a hormone synthesized by the placenta during pregnancy and several other organs, is involved in multiple physiological and pathological conditions. It contributes to the regulation of appetite and body weight. GDF15 induces anorexia and this property can be used in the weight management of obesity and cardiac or cancer cachexia with its analogs and antagonists.