Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus

van den Top, Marco; Lee, Kevin; Whyment, Andrew D; Blanks, Andrew M; Spanswick, David

doi:10.1038/nn1226

Cited by 435Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesNeuropeptides and Animal Physiology

Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus

van den Top, Marco, Lee, Kevin, Whyment, Andrew D, Blanks, Andrew M, Spanswick, David·2004·Nature Neuroscience

DOI 10.1038/nn1226

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Abstract

The hypothalamic arcuate nucleus (ARC) integrates and responds to satiety and hunger signals and forms the origins of the central neural response to perturbations in energy balance. Here we show that rat ARC neurons containing neuropeptide Y (NPY) and agouti-related protein (AgRP), which are conditional pacemakers, are activated by orexigens and inhibited by the anorexigen leptin. We propose a neuron-specific signaling mechanism through which central and peripheral signals engage the central neural anabolic drive.

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Regulation of spontaneous firing of AgRP neurons can be achieved by synaptic and intrinsic mechanisms.
“Regulation of spontaneous firing of AgRP neurons can be achieved by synaptic and intrinsic mechanisms [54, 58–61].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [61]
ATP-sensitive potassium channels were also detected in AgRP neurons.
“ATP-sensitive potassium channels were also detected in AgRP neurons [61].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [61]
Projections from orexin neurons in the lateral hypothalamus activate NPY neurons in the arcuate nucleus.
“Projections from orexin neurons in the lateral hypothalamus activate NPY neurons in the arcuate nucleus.80”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [80]
Orexin neurons are active during waking and quiescent during sleep; consistently, orexin levels in the CSF are maximal at the end of the waking period.
“Orexin neurons are active during waking and quiescent during sleep; consistently, orexin levels in the CSF are maximal at the end of the waking period.80,81”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [80]
Leptin inhibits the firing rate of NPY/AgRP neurons, depolarizes POMC neurons, and activates PI3K signaling in POMC cells.
“leptin inhibits the firing rate of NPY/AgRP neurons (189), while simultaneously depolarizing POMC neurons (42), and also activates PI3K signaling in the latter cells (204).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [189]

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Authors: van den Top, M., Lee, K., Whyment, A. D., Blanks, A. M., & Spanswick, D.
Affiliations: University of Warwick (GB)
Corresponding author: Spanswick, David
ORCID: Lee, Kevin
Blanks, Andrew M
Spanswick, David
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2004-04-18
Volume: 7
Issue: 5
Pages: 493-494
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn1226
OpenAlex: W1974743256
Cited by: 435
References: 15
Citations by year: 2026: 9 · 2025: 10 · 2024: 11 · 2023: 10 · 2022: 12 · 2021: 16 · 2020: 19 · 2019: 22 · 2018: 25 · 2017: 23 · 2016: 28 · 2015: 20 · 2014: 28 · 2013: 33 · 2012: 18
FWCI: 7.98
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: neuropeptide Y, agouti-related protein, arcuate nucleus, hypothalamus, leptin, pacemaker neurons, energy balance, satiety, hunger
MeSH terms: Orexins, Anesthetics, Local, Animals, Arcuate Nucleus of Hypothalamus, Carrier Proteins, Drug Interactions, Male, Membrane Potentials, Neurons, Neuropeptide Y, Neuropeptides, Nickel, Proteins, Receptors, Cell Surface, RNA, Messenger, Tetrodotoxin, 4-Aminopyridine, Rats, Wistar, Receptors, Neuropeptide, Patch-Clamp Techniques, Reverse Transcriptase Polymerase Chain Reaction, Leptin, Potassium Channel Blockers, Intercellular Signaling Peptides and Proteins, Peptide Hormones, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins, Rats, Agouti-Related Protein, Receptors, Leptin, Ghrelin, Orexin Receptors, In Vitro Techniques

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Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus

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