GDF15: A Novel Insight Into Its Biology and Therapeutic Potential in Obesity

Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has recently been identified as a key regulator of appetite homeostasis. Although GDF15 was previously regarded as only a biomarker of disease burden, the discovery of its exclusive receptor, GFRAL, repositioned it as a key mediator of sickness-associated anorexia. The clinical significance of GDF15 and its receptor, GFRAL, is supported by evidence that established weight-loss agents influence circulating GDF15 levels and that GDF15 agonists induce marked weight loss in both preclinical and early-phase clinical studies. This review integrates recent advances in GDF15 biology from evolutionary, mechanistic and translational perspectives, with particular emphasis on its emerging therapeutic potential in obesity.