The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases.
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| Abstract |
MIC-1/GDF15 is a stress response cytokine and a distant member of the transforming growth factor beta (TGFb) superfamily, with no close relatives. It acts via a recently identified receptor called glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL), which is a distant orphan member of the GDNF receptor family that signals through the tyrosine kinase receptor Ret. MIC-1/GDF15 expression and serum levels rise in response to many stimuli that initiate cell stress and as part of a wide variety of disease processes, most prominently cancer and cardiovascular disease. The best documented actions of MIC-1/GDF15 are on regulation of energy homeostasis. When MIC-1/GDF15 serum levels are substantially elevated in diseases like cancer, it subverts a physiological pathway of appetite regulation to induce an anorexia/cachexia syndrome initiated by its actions on hindbrain neurons. These effects make it a potential target for the treatment of both obesity and anorexia/cachexia syndromes, disorders lacking any highly effective, readily accessible therapies.
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| Authors | Vicky W W Tsai, Yasmin Husaini, Amanda Sainsbury, David A Brown, Samuel N Breit |
| Journal | Cell metabolism (Cell Metab) Vol. 28 Issue 3 Pg. 353-368 (09 04 2018) ISSN: 1932-7420 [Electronic] United States |
| PMID | 30184485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review) |
| Copyright | Copyright © 2018 Elsevier Inc. All rights reserved. |
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