ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Leptin modulates the intrinsic excitability of AgRP/NPY neurons in the arcuate nucleus of the hypothalamus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 204 citations in OpenAlex.
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- Neuroendocrine crosstalk between sex and metabolic hormones: mechanisms and implications across the female reproductive spectrum.Discover endocrinology and metabolism · 2026Review
- High-fat diet disrupts a septal control on feeding to promote obesity in male mice.Nature communications · 2025Article
- Aging reveals divergent responses of AgRP/NPY neurons to diet in male and female mice.bioRxiv : the preprint server for biology · 2025Article
- Central leptin pathways in metabolic homeostasis.Clinical science (London, England : 1979) · 2025Review
- Molecular Characterization of Hypothalamic-Pituitary-Ovarian Axis Regulation in the Manchurian Zokor (Genes · 2025Article
- Obesity dysregulates feeding-evoked response dynamics in hypothalamic satiety neurons.Scientific reports · 2025Article
- Brain-Bone Axis in Physiological and Pathological Conditions.International journal of molecular sciences · 2025Review
- Neuroendocrinology and the Genetics of Obesity.Endocrinology · 2025Review
- AgRP neurons shape the sperm small RNA payload.Scientific reports · 2025Article
- Leptin and Associated Neural Pathways Underlying Obesity-Induced Hypertension.Comprehensive Physiology · 2025Review
- Weight cycling exacerbates glucose intolerance and hepatic triglyceride storage in mice with a history of chronic high fat diet exposure.Journal of translational medicine · 2025Article
- Central and peripheral neural circuits regulating glucose homeostasis.npj biomedical innovations · 2025Review
- Article
59 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
The hypothalamic arcuate nucleus (ARH) is a brain region critical for regulation of food intake and a primary area for the action of leptin in the CNS. In lean mice, the adipokine leptin inhibits neuropeptide Y (NPY) and agouti-related peptide (AgRP) neuronal activity, resulting in decreased food intake. Here we show that diet-induced obesity in mice is associated with persistent activation of NPY neurons and a failure of leptin to reduce the firing rate or hyperpolarize the resting membrane potential. However, the molecular mechanism whereby diet uncouples leptin's effect on neuronal excitability remains to be fully elucidated. In NPY neurons from lean mice, the Kv channel blocker 4-aminopyridine inhibited leptin-induced changes in input resistance and spike rate. Consistent with this, we found that ARH NPY neurons have a large, leptin-sensitive delayed rectifier K(+) current and that leptin sensitivity of this current is blunted in neurons from diet-induced obese mice. This current is primarily carried by Kv2-containing channels, as the Kv2 channel inhibitor stromatoxin-1 significantly increased the spontaneous firing rate in NPY neurons from lean mice. In HEK cells, leptin induced a significant hyperpolarizing shift in the voltage dependence of Kv2.1 but had no effect on the function of the closely related channel Kv2.2 when these channels were coexpressed with the long isoform of the leptin receptor LepRb. Our results suggest that dynamic modulation of somatic Kv2.1 channels regulates the intrinsic excitability of NPY neurons to modulate the spontaneous activity and the integration of synaptic input onto these neurons in the ARH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.