Growth/differentiation factor 15 (GDF15/MIC1) is a ~33 kDa protein. Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea and/or loss of appetite. The aversive response is both required to reduce continuing exposure to those stresses at the time of exposure and to promote avoidance behavior in the future. Acts by binding to its receptor, GFRAL, activating GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitutes part of the 'emergency circuit' that shapes responses to stressful conditions. The GDF15-GFRAL signal induces expression of genes involved in metabolism, such as lipid metabolism in adipose tissues. 2. Chung, HK. et al. (2017) The Journal of cell biology 216, 149-165. PMID: 279867973. Wang, T. et al. (2017) EMBO molecular medicine 9, 1150-1164. PMID: 285720904. Mullican, SE. et al. (2017) Nature medicine 23, 1150-1157. PMID: 288460975. Emmerson, PJ. et al. (2017) Nature medicine 23, 1215-1219. PMID: 288460986. Yang, L. et al. (2017) Nature medicine 23, 1158-1166. PMID: 288460998. Tsai, VW. et al. (2018) International journal of obesity (2005) 42, 561-571. PMID: 290262149. Xiong, Y. et al. (2017) Science translational medicine 9. PMID: 2904643510. Patel, S. et al. (2019) Cell metabolism 29, 707-718.e8. PMID: 30639358 | 
