Journal article

The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling

Amy A Worth, Rosemary Shoop, Katie Tye, Claire H Feetham, Giuseppe D'Agostino, Garron T Dodd, Frank Reimann, Fiona M Gribble, Emily C Beebe, James D Dunbar, Jesline T Alexander-Chacko, Dana K Sindelar, Tamer Coskun, Paul J Emmerson, Simon M Luckman



The cytokine, GDF15, is produced in pathological states which cause cellular stress, including cancer. When over expressed, it causes dramatic weight reduction, suggesting a role in disease-related anorexia. Here, we demonstrate that the GDF15 receptor, GFRAL, is located in a subset of cholecystokinin neurons which span the area postrema and the nucleus of the tractus solitarius of the mouse. GDF15 activates GFRALAP/NTS neurons and supports conditioned taste and place aversions, while the anorexia it causes can be blocked by a monoclonal antibody directed at GFRAL or by disrupting CCK neuronal signalling. The cancer-therapeutic drug, cisplatin, induces the release of GDF15 and activates GFRA..

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University of Melbourne Researchers


Awarded by Biotechnology and Biological Sciences Research Council

Awarded by Medical Research Council

Funding Acknowledgements

Biotechnology and Biological Sciences Research Council BB/M001067/1 Simon M LuckmanBiotechnology and Biological Sciences Research Council BB/L021129/1 Simon M LuckmanMedical Research Council MR/R002991/1 Simon M LuckmanMedical Research Council MR/P009824/2 Giuseppe D'AgostinoBiotechnology and Biological Sciences Research Council BB/S008098/1 Simon M LuckmanUniversity of Manchester PhD Scholarship Rosemary ShoopThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.