{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["9"],"submitter":["Worth AA"],"funding":["Medical Research Council","Biotechnology and Biological Sciences Research Council"],"pubmed_abstract":["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 GFRALAP/NTS neurons, as well as causing significant reductions in food intake and body weight in mice. These metabolic effects of cisplatin are abolished by pre-treatment with the GFRAL monoclonal antibody. Our results suggest that GFRAL neutralising antibodies or antagonists may provide a co-treatment opportunity for patients undergoing chemotherapy."],"journal":["eLife"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7410488"],"repository":["biostudies-literature"],"pubmed_title":["The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling."],"pmcid":["PMC7410488"],"funding_grant_id":["BB/M001067/1","MR/R002991/1","MR/P009824/2","BB/S008098/1","BB/L021129/1"],"pubmed_authors":["Shoop R","Feetham CH","Gribble FM","Dodd GT","Worth AA","Reimann F","Coskun T","Sindelar DK","Dunbar JD","Emmerson PJ","Tye K","Beebe EC","Alexander-Chacko JT","D'Agostino G","Luckman SM"],"additional_accession":[]},"is_claimable":false,"name":"The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling.","description":"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 GFRALAP/NTS neurons, as well as causing significant reductions in food intake and body weight in mice. These metabolic effects of cisplatin are abolished by pre-treatment with the GFRAL monoclonal antibody. Our results suggest that GFRAL neutralising antibodies or antagonists may provide a co-treatment opportunity for patients undergoing chemotherapy.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2021-02-19T10:05:31Z","creation":"2020-08-15T07:04:25Z"},"accession":"S-EPMC7410488","cross_references":{"pubmed":["32723474"],"doi":["10.7554/eLife.55164"]}}