GDF-15/MIC-1 Protein, Human

GDF15 (Growth Differentiation Factor 15) is a divergent member of the Transforming Growth Factor-β (TGF-β) superfamily. Initially identified in activated macrophages, it is a stress-induced cytokine whose expression is upregulated under conditions such as tissue hypoxia, inflammation, acute injury, and oxidative stress. GDF15 is highly expressed in the placenta and prostate and acts as a pleiotropic cytokine involved in the cellular stress response program.

Functionally, GDF15 signals through its specific receptor, GFRAL (GDNF Family Receptor Alpha Like), which is primarily expressed in the area postrema and nucleus tractus solitarius of the brainstem. Upon binding, GDF15 recruits the co-receptor RET to initiate signaling. This axis constitutes an "emergency circuit" that regulates feeding responses to metabolic and toxin-induced stresses, modulating food intake, energy expenditure, and body weight. GDF15 also promotes nausea and vomiting, with elevated levels linked to pregnancy-induced morning sickness and hyperemesis gravidarum.