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Action of GDF15 under conditions of chronic stress. Circulating GDF15 increases in response to various cellular stresses and crosses the blood-brain barrier. GDF15 binds to GFRAL and activates RET in neurons in the hindbrain area postrema (AP) and nucleus of the solitary tract (NTS). This central pathway leads to reduced food intake, causing loss of lean body mass and anorexia-cachexia syndrome.
