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
ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2020
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..View full abstract
Awarded by Biotechnology and Biological Sciences Research Council
Awarded by Medical Research Council
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.