CaMK1D signaling in AgRP neurons promotes ghrelin-mediated food intake
Vivot, K.; Meszaros, G.; Zhang, Z.; Erbs, E.; Yeghiazaryan, G.; Quinones, M.; Grandgirard, E.; Schneider, A.; Clauss--Creusot, E.; Charlet, A.; Faour, M.; Martin, C.; Luquet, S.; Kloppenburg, P.; Nogueiras, R.; Ricci, R.
Show abstract
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 diet-induced 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. HighlightsO_LIWhole-body deletion of CaMK1D in mice reduces food intake, ghrelin sensitivity and protects against obesity. C_LIO_LIAgRP/NPY neuron-specific deletion of CaMK1D reduces food intake, ghrelin sensitivity, energy expenditure and protects against obesity. C_LIO_LICaMK1D is dispensable for ghrelin-stimulated electrical activity of AgRP neurons and hypothalamic AMPK signaling. C_LIO_LICaMK1D controls phosphorylation of CREB and CREB-dependent expression of the orexigenic neuropeptides AgRP and NPY. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=174 HEIGHT=200 SRC="FIGDIR/small/471546v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@40d7d7org.highwire.dtl.DTLVardef@11a8c64org.highwire.dtl.DTLVardef@1f6fad3org.highwire.dtl.DTLVardef@1cd5581_HPS_FORMAT_FIGEXP M_FIG C_FIG
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Drp1 Is Required For Agrp Neuronal Activity And Feeding 97%
- Smith-Magenis syndrome protein RAI1 regulates body weight homeostasis through hypothalamic BDNF-producing neurons and neurotrophin downstream signalling 97%
- Control of brown adipose tissue adaptation to nutrient stress by the activin receptor ALK7 96%
Similar papers in this journal
- Inhibition of Mitochondrial Fission and iNOS in the Dorsal Vagal Complex Protects from Overeating and Weight Gain 96%
- Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis 96%
- Ghrelin signalling in AgRP neurons links metabolic state to the sensory regulation of AgRP neural activity. 95%
Similar papers in this journal
- Bromodomain inhibition reveals FGF15/19 as a target of epigenetic regulation and metabolic control 95%
- Prostaglandin PGE2 receptor EP4 regulates microglial phagocytosis and increases susceptibility to diet-induced obesity 95%
- Withaferin A promotes white adipose browning and prevents obesity through sympathetic nerve-activated Prdm16-FATP1 axis 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.