Growth differentiation factor 15 (GDF-15) is a divergent member of the transforming growth factor β (TGF-β) superfamily. GDF-15 is synthesized as a 40 kDa precursor and is then proteolytically cleaved to be released as a disulfide-linked homodimer that is biologically active. The expression of GDF-15 is dramatically increased in many types of cancer. Tumor overproduction of GDF-15 induces appetite suppression and subsequent weight loss. Overexpression or pharmacological infusion of GDF15 reduces food intake and body weight and improves metabolic profiles in various metabolic disease models in both rodents and monkeys. GDF15 activates ERK1/2 and Akt pathway via binding to its receptor GDNF receptor α-like (GFRAL). Therefore, GDF15 has been proposed to be a potential target for the maintenance of energy homeostasis and treatment of tumor anorexia, as well as of obesity.
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