GDF15: A hormone conveying somatic distress to the brain.

GDF15: A hormone conveying somatic distress to the brain. Endocr Rev. 2020 Apr 20;: Authors: Lockhart SM, Saudek V, O'Rahilly S Abstract GDF15 has recently gained scientific and translational prominence with the discovery that its receptor is a GFRAL-RET heterodimer of which GFRAL is expressed solely in the hindbrain. Activation of this receptor results in reduced food intake and loss of body weight and is perceived and recalled by animals as aversive. This information encourages a revised interpretation of the large body of previous research on the protein. GDF15 can be secreted by a wide variety of cell types in response to a broad range of stressors. We propose that central sensing of GDF15 via GFRAL-RET activation results in behaviors that facilitate the reduction of exposure to a noxious stimulus. The human trophoblast appears to have hi-jacked this signal, producing large amounts of GDF15 from early pregnancy. We speculate that this encourages avoidance of potential teratogens in pregnancy. Circulating GDF15 levels are elevated in a range of human disease states including various forms of cachexia, and GDF15-GFRAL antagonism is emerging as a therapeutic strategy for anorexia-cachexia syndromes. Metformin elevates circulating GDF15 chronically in man and the weight loss caused by this drug appears to be dependent on the rise in GDF15. This supports the concept that chronic activation of the GDF15-GFRAL axis has efficacy as an an...
Source: Endocrine Reviews - Category: Endocrinology Tags: Endocr Rev Source Type: research