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.

• Authors: 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
• Journal: Nature metabolism (Nat Metab) Vol. 5 Issue 6 Pg. 1045-1058 (06 2023) ISSN: 2522-5812 [Electronic] Germany
• PMID: 37277610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Ghrelin
• Agouti-Related Protein
• Neuropeptide Y
• Camk1d protein, mouse
• Calcium-Calmodulin-Dependent Protein Kinase Type 1

Topics

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