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. 2023 Jun;5(6):1045-1058.
doi: 10.1038/s42255-023-00814-x. Epub 2023 Jun 5.

CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake

Karl Vivot  1   2   3   4 , Gergö Meszaros  5   6   7   8 , Evanthia Pangou  5   6   7   8 , Zhirong Zhang  5   6   7   8 , Mengdi Qu  5   6   7   8 , Eric Erbs  5   6   7   8 , Gagik Yeghiazaryan  9 , Mar Quiñones  10   11 , Erwan Grandgirard  5   6   7   8 , Anna Schneider  5   6   7   8 , Etienne Clauss-Creusot  8   12 , Alexandre Charlet  8   12 , Maya Faour  13 , Claire Martin  13 , Fedor Berditchevski  14 , Izabela Sumara  5   6   7   8 , Serge Luquet  13 , Peter Kloppenburg  9 , Ruben Nogueiras  10   15 , Romeo Ricci  16   17   18   19   20
Affiliations

CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake

Karl Vivot et al. Nat Metab. 2023 Jun.

Abstract

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.

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