| First Author | Worth AA | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32723474 | Mgi Jnum | J:298668 |
| Mgi Id | MGI:6477067 | Doi | 10.7554/eLife.55164 |
| Citation | Worth AA, et al. (2020) The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling. Elife 9:e55164 |
| abstractText | 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 GFRAL(AP/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 GFRAL(AP/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. |
