The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling.
Elife
; 92020 07 29.
Article
em En
| MEDLINE
| ID: mdl-32723474
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.
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MEDLINE
Assunto principal:
Tronco Encefálico
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Transdução de Sinais
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Anorexia
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Pica
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Fator 15 de Diferenciação de Crescimento
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Neurônios
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article