Targeting the GDF15 Signalling for Obesity Treatment: Recent Advances and Emerging Challenges

The growth differentiation factor 15 (GDF15)-glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL) pathway plays a crucial role in the regulation of metabolism, appetite and body weight control. Obesity is an increasingly prevalent chronic disease worldwide, necessitating effective treatment strategies. Recent preclinical and clinical studies have highlighted that targeting the GDF15-GFRAL signalling pathway is a promising approach for treating obesity, particularly because it has minimal impact on skeletal muscle mass, which is essential to preserve during weight loss. Given its distinctive mechanisms, the GDF15-GFRAL axis represents an attractive target for addressing various metabolic disorders, especially obesity. In this review, we will explore how the GDF15-GFRAL axis is regulated, its distribution in the body and its role in the regulation of metabolism, appetite and obesity. Additionally, we will discuss recent advances and potential challenges in targeting the GDF15-GFRAL axis for obesity treatment.