Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation
| العنوان: | Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation |
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| المؤلفون: | Paul J. Emmerson, David J. Hodson, Brandy M. Snider, Nicolas Nunn, Tamer Coskun, Jenna Hunter, Mehdi Boutagouga Boudjadja, Gabriella Aviello, Isabella Culotta, Minrong Ai, Simon M. Luckman, Alessia Costa, Giuseppe D'Agostino, Lourdes Valencia-Torres |
| المساهمون: | Costa, A., Ai, M., Nunn, N., Culotta, I., Hunter, J., Boudjadja, M. B., Valencia-Torres, L., Aviello, G., Hodson, D. J., Snider, B. M., Coskun, T., Emmerson, P. J., Luckman, S. M., D'Agostino, G. |
| المصدر: | Costa, A, Ai, M, Nunn, N, Culotta, I, Hunter, J, Boudjadja, M B, Valencia-Torres, L, Aviello, G, Hodson, D J, Snider, B M, Coskun, T, Emmerson, P J, Luckman, S M & D'Agostino, G 2021, ' Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation ', Molecular Metabolism, vol. 55, 101407 . https://doi.org/10.1016/j.molmet.2021.101407Test Molecular Metabolism Molecular Metabolism, Vol 55, Iss, Pp 101407-(2022) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Blood Glucose, Male, Glucagon-like peptide-1, endocrine system, Glucose-dependent insulinotropic polypeptide, media_common.quotation_subject, Appetite, Gastric Inhibitory Polypeptide, Brief Communication, Glucagon-Like Peptide-1 Receptor, Receptors, Gastrointestinal Hormone, Mice, Nucleus of the solitary tract, Glucagon-Like Peptide 1, Appetite Depressants, Medicine, Animals, Hypoglycemic Agents, Insulin, Receptor, Internal medicine, Molecular Biology, Glucagon-like peptide 1 receptor, media_common, Cholecystokinin, Neurons, business.industry, Area postrema, digestive, oral, and skin physiology, Brain, Nausea, Cell Biology, Liraglutide, Glucagon, RC31-1245, Mice, Inbred C57BL, Anorectic, Exenatide, Female, Brainstem, business, Neuroscience, hormones, hormone substitutes, and hormone antagonists |
| الوصف: | Objective Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective medications to reduce appetite and body weight. These actions are centrally mediated; however, the neuronal substrates involved are poorly understood. Methods We employed a combination of neuroanatomical, genetic, and behavioral approaches in the mouse to investigate the involvement of caudal brainstem cholecystokinin-expressing neurons in the effect of the GLP-1RA exendin-4. We further confirmed key neuroanatomical findings in the non-human primate brain. Results We found that cholecystokinin-expressing neurons in the caudal brainstem are required for the anorectic and body weight-lowering effects of GLP-1RAs and for the induction of GLP-1RA-induced conditioned taste avoidance. We further show that, while cholecystokinin-expressing neurons are not a direct target for glucose-dependent insulinotropic peptide (GIP), GIP receptor activation results in a reduced recruitment of these GLP-1RA-responsive neurons and a selective reduction of conditioned taste avoidance. Conclusions In addition to disclosing a neuronal population required for the full appetite- and body weight-lowering effect of GLP-1RAs, our data also provide a novel framework for understanding and ameliorating GLP-1RA-induced nausea — a major factor for withdrawal from treatment. Highlights • CCKAP/NTS neurons are required for the full anorectic and body weight-lowering effect of GLP-1 receptor agonists. • GLP-1 receptor agonists promote the formation of conditioned taste avoidance by activating CCKAP/NTS neurons. • CCKAP/NTS neurons are not activated in response to GIP receptor agonists. • GIP receptor agonists reduce GLP-1 receptor agonist-induced neuronal responses in the caudal brainstem. • GIP receptor agonists reduce GLP-1 receptor agonist-induced conditioned taste avoidance. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3c8f4b8195f8ad7f7f17bc35a2d9541Test https://www.research.manchester.ac.uk/portal/en/publications/anorectic-and-aversive-effects-of-glp1-receptor-agonism-are-mediated-by-brainstem-cholecystokinin-neurons-and-modulated-by-gip-receptor-activationTest(97b025ca-ff46-4b48-a59c-edf8df09098e).html |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f3c8f4b8195f8ad7f7f17bc35a2d9541 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |