The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling
| العنوان: | The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling |
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| المؤلفون: | Tamer Coskun, Claire H. Feetham, Giuseppe D'Agostino, Garron T. Dodd, Amy A. Worth, Frank Reimann, James D. Dunbar, Fiona M. Gribble, Simon M. Luckman, Paul J. Emmerson, Katie Tye, Emily C Beebe, Dana Sindelar, Jesline T. Alexander-Chacko, Rosemary Shoop |
| المساهمون: | Worth, Amy A [0000-0003-2573-7140], Shoop, Rosemary [0000-0002-3617-4358], Luckman, Simon M [0000-0001-5318-5473], Apollo - University of Cambridge Repository |
| المصدر: | Worth, A A, Shoop, R, Tye, K, Feetham, C H, D'Agostino, G, Dodd, G T, Reimann, F, Gribble, F M, Beebe, E C, Dunbar, J D, Alexander-Chacko, J T, Sindelar, D K, Coskun, T, Emmerson, P J & Luckman, S M 2020, ' The cytokine GDF15 signals through a population of brainstem cholecystokinin neurons to mediate anorectic signalling ', eLife, vol. 9, e55164, pp. 1-19 . https://doi.org/10.7554/eLife.55164Test eLife, Vol 9 (2020) eLife |
| بيانات النشر: | eLife Sciences Publications, Ltd, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, food intake, Lydia Becker Institute, medicine.medical_treatment, cisplatin, brainstem, neuroscience, Rats, Sprague-Dawley, Mice, Random Allocation, 0302 clinical medicine, rat, Biology (General), Receptor, Cholecystokinin, Neurons, education.field_of_study, GFRAL, General Neuroscience, Area postrema, General Medicine, Recombinant Proteins, Anorexia, Cytokine, Pica, Medicine, medicine.symptom, Signal transduction, Research Article, Signal Transduction, medicine.medical_specialty, Growth Differentiation Factor 15, QH301-705.5, Science, Population, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, medicine, Animals, education, mouse, General Immunology and Microbiology, CCK, Rats, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, GDF15, nervous system, Anorectic, 030217 neurology & neurosurgery, Brain Stem |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| DOI: | 10.17863/cam.56562 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c36fee4c12ae9aa6d1944526e39affeTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2c36fee4c12ae9aa6d1944526e39affe |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.17863/cam.56562 |
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