CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake

Karl Vivot; Gergö Meszaros; Evanthia Pangou; Zhirong Zhang; Mengdi Qu; Eric Erbs; Gagik Yeghiazaryan; Mar Quiñones; Erwan Grandgirard; Anna Schneider; Etienne Clauss-Creusot; Alexandre Charlet; Maya Faour; Claire Martin; Fedor Berditchevski; Izabela Sumara; Serge Luquet; Peter Kloppenburg; Ruben Nogueiras; Romeo Ricci

doi:10.1038/s42255-023-00814-x

CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake

Karl Vivot^*, Gergö Meszaros, Evanthia Pangou, Zhirong Zhang, Mengdi Qu, Eric Erbs, Gagik Yeghiazaryan, Mar Quiñones, Erwan Grandgirard, Anna Schneider, Etienne Clauss-Creusot, Alexandre Charlet, Maya Faour, Claire Martin, Fedor Berditchevski, Izabela Sumara, Serge Luquet, Peter Kloppenburg, Ruben Nogueiras, Romeo Ricci^*

^*Corresponding author for this work

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1045-1058
Number of pages	14
Journal	Nature metabolism
Volume	5
Issue number	6
DOIs	https://doi.org/10.1038/s42255-023-00814-x
Publication status	Published - 5 Jun 2023

Bibliographical note

Keywords

Mice
Animals
Male
Ghrelin/metabolism
Agouti-Related Protein/genetics
Diabetes Mellitus, Type 2/metabolism
Neuropeptide Y/genetics
Neurons/metabolism
Obesity/metabolism
Mice, Knockout
Eating
Calcium-Calmodulin-Dependent Protein Kinase Type 1/metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s42255-023-00814-x

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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. (2023). CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake. Nature metabolism, 5(6), 1045-1058. https://doi.org/10.1038/s42255-023-00814-x

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title = "CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake",

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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author = "Karl Vivot and Gerg{\"o} Meszaros and Evanthia Pangou and Zhirong Zhang and Mengdi Qu and Eric Erbs and Gagik Yeghiazaryan and Mar Qui{\~n}ones and Erwan Grandgirard and Anna Schneider and Etienne Clauss-Creusot and Alexandre Charlet and Maya Faour and Claire Martin and Fedor Berditchevski and Izabela Sumara and Serge Luquet and Peter Kloppenburg and Ruben Nogueiras and Romeo Ricci",

note = "{\textcopyright} 2023. The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2023",

month = jun,

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doi = "10.1038/s42255-023-00814-x",

language = "English",

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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 2023, 'CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake', Nature metabolism, vol. 5, no. 6, pp. 1045-1058. https://doi.org/10.1038/s42255-023-00814-x

TY - JOUR

T1 - CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake

AU - Vivot, Karl

AU - Meszaros, Gergö

AU - Pangou, Evanthia

AU - Zhang, Zhirong

AU - Qu, Mengdi

AU - Erbs, Eric

AU - Yeghiazaryan, Gagik

AU - Quiñones, Mar

AU - Grandgirard, Erwan

AU - Schneider, Anna

AU - Clauss-Creusot, Etienne

AU - Charlet, Alexandre

AU - Faour, Maya

AU - Martin, Claire

AU - Berditchevski, Fedor

AU - Sumara, Izabela

AU - Luquet, Serge

AU - Kloppenburg, Peter

AU - Nogueiras, Ruben

AU - Ricci, Romeo

PY - 2023/6/5

Y1 - 2023/6/5

N2 - 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.

AB - 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.

KW - Mice

KW - Animals

KW - Male

KW - Ghrelin/metabolism

KW - Agouti-Related Protein/genetics

KW - Diabetes Mellitus, Type 2/metabolism

KW - Neuropeptide Y/genetics

KW - Neurons/metabolism

KW - Obesity/metabolism

KW - Mice, Knockout

KW - Eating

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 1/metabolism

UR - https://www.scopus.com/pages/publications/85160860649

U2 - 10.1038/s42255-023-00814-x

DO - 10.1038/s42255-023-00814-x

M3 - Article

C2 - 37277610

SN - 2522-5812

VL - 5

SP - 1045

EP - 1058

JO - Nature metabolism

JF - Nature metabolism

IS - 6

ER -

CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake

Abstract

Bibliographical note

Keywords

UN SDGs

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