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Pré-Publication, Document De Travail Année : 2022

CaMK1D signaling in AgRP neurons promotes ghrelin-mediated food intake

Serge Luquet

Résumé

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.
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Dates et versions

hal-03795873 , version 1 (04-10-2022)

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  • HAL Id : hal-03795873 , version 1

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Kevin Vivot, Gergö Meszaros, Zhirong Zhang, Eric Erbs, Gagik Yeghiazaryan, et al.. CaMK1D signaling in AgRP neurons promotes ghrelin-mediated food intake. 2022. ⟨hal-03795873⟩
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