Metabolic Messenger: growth differentiation factor 15

Growth differentiation factor 15 (GDF15; also known as macrophage-inhibitory cytokine-1) is a stress-responsive cytokine that is overexpressed under a broad range of conditions. It has a role in regulating appetite and body weight and is an aetiological factor in anorexia-cachexia syndromes, as well as nausea and vomiting during pregnancy. Long after its original cloning, its receptor was identified as GFRAL, a distant member of the GDNF receptor family within the TGFβ superfamily, with RET as its co-receptor. Both of these are highly localized to specific hindbrain regions. Although many of GFRAL's metabolic changes may be linked to its effect on suppressing appetite, recent findings suggest that GDF15 also independently regulates energy expenditure and insulin sensitivity. Here, we review recent literature and provide updates on the current understanding of GDF15 biology and its therapeutic applications in health and metabolic diseases.