| Autor: |
Vivot, Kevin, Meszaros, Gergö, Zhang, Zhirong, Erbs, Eric, Yeghiazaryan, Gagik, Quiñones, Mar, Grandgirard, Erwan, Schneider, Anna, Clauss--Creusot, Etienne, Charlet, Alexandre, Faour, Maya, Martin, Claire, Luquet, Serge, Kloppenburg, Peter, Nogueiras, Ruben, Ricci, Romeo |
| Přispěvatelé: |
Charlet, Alexandre, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Cologne, Instituto de Investigación Sanitaria de Santiago de Compostela / Health Research Institute of Santiago de Compostela (IDIS), CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III [Madrid] (ISC), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Popis: |
Hypothalamic AgRP/NPY neurons are key players in the control of feeding behavior. Ghrelin, a major hormone released under fasting conditions, activates orexigenic AgRP/NPY neurons to stimulate food intake and adiposity. However, cell-autonomous ghrelin-dependent signaling mechanisms in AgRP/NPY neurons remain poorly defined. Here we demonstrate that calcium/calmodulin-dependent protein kinase ID (CaMK1D), a genetic hot spot in type 2 diabetes, is activated in hypothalamus upon ghrelin stimulation and acts in AgRP neurons to promote ghrelin-dependent food intake. Global CaMK1D knockout mice are resistant to the orexigenic action of ghrelin, gain less body weight and are protected against high-fat dietinduced obesity. Deletion of CaMK1D in AgRP but not in POMC neurons is sufficient to recapitulate above phenotypes. Lack of CaMK1D attenuates phosphorylation of CREB and CREB-dependent expression of the orexigenic neuropeptides AgRP/NPY as well as the amount of AgRP fiber projections to the Paraventricular nucleus (PVN), while electrical activity of AgRP neurons and 5' AMP-activated protein kinase (AMPK) signaling are unaffected. Hence, CaMK1D links ghrelin action to transcriptional control of orexigenic neuropeptide availability in AgRP neurons. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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