Fiche publication
Date publication
juin 2023
Journal
Nature metabolism
Auteurs
Membres identifiés du Cancéropôle Est :
Pr RICCI Roméo
,
Dr SUMARA Izabela
,
Dr PANGOU Evanthia
Tous les auteurs :
Vivot K, Meszaros G, Pangou E, Zhang Z, Qu M, Erbs E, Yeghiazaryan G, Quiñones M, Grandgirard E, Schneider A, Clauss-Creusot E, Charlet A, Faour M, Martin C, Berditchevski F, Sumara I, Luquet S, Kloppenburg P, Nogueiras R, Ricci R
Lien Pubmed
Résumé
Hypothalamic AgRP/NPY neurons are key players in the control of feeding behaviour. Ghrelin, a major orexigenic hormone, activates AgRP/NPY neurons to stimulate food intake and adiposity. However, cell-autonomous ghrelin-dependent signalling mechanisms in AgRP/NPY neurons remain poorly defined. Here we show that calcium/calmodulin-dependent protein kinase ID (CaMK1D), a genetic hot spot in type 2 diabetes, is activated upon ghrelin stimulation and acts in AgRP/NPY neurons to mediate ghrelin-dependent food intake. Global Camk1d-knockout male mice are resistant to ghrelin, gain less body weight and are protected against high-fat-diet-induced obesity. Deletion of Camk1d in AgRP/NPY, but not in POMC, neurons is sufficient to recapitulate above phenotypes. In response to ghrelin, lack of CaMK1D attenuates phosphorylation of CREB and CREB-dependent expression of the orexigenic neuropeptides AgRP/NPY in fibre projections to the paraventricular nucleus (PVN). Hence, CaMK1D links ghrelin action to transcriptional control of orexigenic neuropeptide availability in AgRP neurons.
Référence
Nat Metab. 2023 06 5;:
