GDF15 is still a mystery hormone

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) superfamily. Despite its identification over 20 years ago, the functions of GDF15 remain complex and not fully elucidated. Its concentration in plasma varies widely depending on the physiological and pathophysiological state of the organism. GDF15 has been described to regulate food intake and insulin sensitivity in rodents via the GDNF family receptor α-like (GFRAL) receptor, and to be elevated in pregnancy and many disease states and decreased in physically fit individuals. We discuss the latest developments in the regulation of GDF15 secretion and its diverse physiological effects, and touch upon possible GFRAL-independent effects of GDF15. In addition, we discuss the effects of proteins and peptides derived from the same precursor protein as GDF15.