Affinage

AGRP

Agouti-related protein · UniProt O00253

Length
132 aa
Mass
14.4 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AGRP encodes an orexigenic neuropeptide produced predominantly by hypothalamic arcuate nucleus AgRP neurons, whose activity is both necessary and sufficient to drive feeding, lower energy expenditure, and increase fat stores (PMID:21364278). As a secreted ligand, AgRP acts at melanocortin receptors as an inverse agonist of MC3R/MC4R constitutive activity and an antagonist of α-MSH/ACTH, an activity modulated by MRAP2 (PMID:28512117); MC3R expressed cell-autonomously on AgRP neurons themselves is in turn required to relay fasting, cold, and ghrelin signals into neuronal activation (PMID:37792535). The behavioral output of these neurons is carried by co-released transmitters with division of labor: NPY is uniquely required for the long-lasting feeding response and signals through NPY1R for food intake and respiratory quotient and NPY2R for energy expenditure and locomotion (PMID:31033437, PMID:35167990), while GABAergic output to the parabrachial nucleus prevents lethal anorexia and inhibits lateral hypothalamic orexin neurons (PMID:21211531, PMID:32667686). AgRP transcription and neuronal excitability are governed by a leptin/insulin-responsive transcriptional axis in which FOXO1 activates Agrp through coactivator–corepressor exchange opposed by STAT3, acting via the downstream effector Gpr17 (PMID:16604086, PMID:26180086), reinforced by cis-regulatory elements upstream of the gene (PMID:15345681) and by epigenetic control through TET3-mediated promoter 5-hydroxymethylcytosine and Dnmt3a-dependent methylation (PMID:36189793, PMID:31792207). Acute energy-state signals converge on these neurons through AMPK–PAK-driven synaptic plasticity during fasting (PMID:27321921), ghrelin–CaMK1D–CREB signaling (PMID:37277610), asprosin–Ptprd–SK3 channel coupling (PMID:36812308), and circadian timing imposed by the suprachiasmatic nucleus (PMID:37957320). Beyond feeding, AgRP neuron output controls whole-body substrate utilization and lipogenesis (PMID:30659173), fasting-induced hepatic autophagy via an NPY→PVH→corticosterone/glucocorticoid receptor axis (PMID:37075752), hepatic glucose production through insulin receptor signaling (PMID:28385803), bone metabolism via sympathetic tone and a PDK1–FoxO1–GHRH–GH–IGF1 axis (PMID:26411686, PMID:28462077), and systemic TNF-α release during endotoxemia through neuronal glucocorticoid receptor (PMID:36182699).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2004 High

    Establishing how Agrp achieves its arcuate-restricted, fasting-responsive expression localized the regulatory logic to defined cis-elements before the trans-acting machinery was known.

    Evidence BAC reporter transgenic deletion series with fasting challenge in mice; conserved zebrafish hypothalamic fasting-induced expression

    PMID:14709799 PMID:15345681

    Open questions at the time
    • Did not identify the transcription factors binding the conserved regions
    • Conservation across vertebrates inferred, not the full enhancer architecture
  2. 2006 High

    Identifying FOXO1 and STAT3 as opposing regulators of the Agrp promoter explained how leptin and fasting bidirectionally tune AgRP transcription at the molecular level.

    Evidence Adenoviral delivery of constitutively nuclear or transactivation-deficient FoxO1 to arcuate nucleus with promoter coactivator/corepressor exchange assays

    PMID:16604086

    Open questions at the time
    • Downstream effectors of FOXO1 not defined here
    • Did not address neuronal excitability versus transcription
  3. 2011 High

    Bidirectional chemogenetic control established AgRP neuron activity as both necessary and sufficient for feeding, and ablation/rescue pinpointed GABAergic output to the PBN as the survival-critical signal.

    Evidence DREADD activation/inhibition with metabolic readouts; diphtheria toxin ablation with PBN GABA-A agonist rescue

    PMID:21211531 PMID:21364278

    Open questions at the time
    • Did not resolve the contribution of individual co-transmitters
    • Mechanism of MC4R-independent anorexia prevention left open
  4. 2016 High

    Linking fasting to AMPK–PAK signaling explained the acute structural plasticity that increases AgRP neuron excitability during energy deficit.

    Evidence Neuron-specific AMPK manipulation, spine counting, and electrophysiology in AgRP neurons

    PMID:27321921

    Open questions at the time
    • Upstream activator of AMPK during fasting not fully defined
    • Link between spinogenesis and feeding output indirect
  5. 2017 Medium

    In vitro receptor pharmacology defined AgRP as a melanocortin receptor inverse agonist/antagonist whose activity is modulated by MRAP2, and revealed expression and signaling outside the hypothalamus.

    Evidence CHO-cell luciferase reporter and co-IP for cMC3R/cMC4R and MRAP2; adrenal chromaffin cell expression and electrophysiology; insulin-receptor competition by heparin

    PMID:28512117 PMID:28531318 PMID:28877477

    Open questions at the time
    • Receptor assays performed in chicken ortholog and heterologous cells
    • Physiological significance of adrenal AgRP not established
    • Heparin–insulin receptor competition is a single-lab finding
  6. 2019 High

    Conditional knockout and rescue dissected the co-transmitter code, showing NPY (not AgRP peptide or GABA) drives sustained feeding, while parallel work linked AgRP neurons to substrate utilization and hepatic insulin action.

    Evidence Conditional NPY/AgRP/GABA knockouts with selective NPY rescue; indirect calorimetry with FAS inhibition; insulin-receptor conditional knockout with euglycemic clamps

    PMID:28385803 PMID:30659173 PMID:31033437

    Open questions at the time
    • How NPY produces a long-lasting versus acute signal not resolved
    • Tissue site of altered substrate utilization not fully mapped
  7. 2022 High

    Epigenetic and receptor-level work showed TET3-mediated 5hmC dynamically silences Agrp in response to leptin and that NPY's two receptors segregate feeding from energy expenditure.

    Evidence CRISPR Tet3 knockout with ChIP/5hmC assays; conditional Npy knockout with NPY1R/NPY2R-selective ligand rescue

    PMID:35167990 PMID:36189793

    Open questions at the time
    • Identity of the TET3-associated chromatin-modifying complex not fully defined
    • How leptin recruits TET3 to the promoter unresolved
  8. 2023 High

    Multiple studies mapped the acute signaling inputs (ghrelin–CaMK1D–CREB, asprosin–Ptprd–SK3, MC3R) and downstream physiological outputs (hepatic autophagy, immune TNF-α control) of AgRP neurons, and reframed their rhythm as circadian rather than purely deprivation-driven.

    Evidence Cell-type-specific conditional knockouts of Camk1d, Ptprd/SK3, MC3R, and glucocorticoid receptor; NPY→PVH→corticosterone circuit mapping; SCN lesion with optogenetics

    PMID:36182699 PMID:36812308 PMID:37075752 PMID:37277610 PMID:37792535 PMID:37957320

    Open questions at the time
    • Integration of multiple convergent signaling pathways at the single-neuron level not modeled
    • Several downstream outputs (autophagy, TNF-α) characterized in single labs
  9. 2024 Medium

    Identification of intracellular bioenergetic and metal-handling regulators (miR-33, transferrin-receptor-mediated iron) extended AgRP neuron control to mitochondrial and oxidative-stress pathways governing obesity.

    Evidence AgRP-specific conditional knockouts of miR-33 and Tfrc with metabolic phenotyping and ER stress/NF-κB markers

    PMID:38459068 PMID:38460132

    Open questions at the time
    • Causal chain from iron/oxidative stress to neuronal activity is correlative in parts
    • Single-lab findings awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many convergent transcriptional, epigenetic, metabolic, and synaptic inputs are integrated within a single AgRP neuron to produce graded behavioral output, and the function of AgRP protein itself versus the neuron's co-transmitters in humans, remain unresolved.
  • No structural model of AgRP–MC3R/MC4R engagement in the timeline
  • Relative human in vivo contribution of AgRP peptide versus NPY/GABA unestablished
  • No Mendelian disease link in the available corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-112316 Neuronal System 2 R-HSA-1430728 Metabolism 2
Partners
MC3RMC4RMRAP2

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 Chemogenetic (DREADD) activation of AgRP neurons in mice is sufficient to rapidly and dramatically induce feeding, reduce energy expenditure, and increase fat stores; conversely, inhibiting AgRP neuron activity in hungry mice reduced food intake, demonstrating AgRP neuron activity is both necessary and sufficient for feeding. DREADD chemogenetic activation/inhibition in vivo with behavioral and metabolic readouts The Journal of clinical investigation High 21364278
2006 FoxO1, a transcription factor, directly regulates Agrp expression in hypothalamic arcuate neurons downstream of leptin signaling; constitutively nuclear FoxO1 blocks leptin's ability to suppress Agrp, while a transactivation-deficient FoxO1 prevents fasting-induced Agrp induction. FoxO1 and STAT3 exert opposing actions on Agrp and Pomc promoters, with FoxO1 promoting coactivator-corepressor exchange that activates Agrp and inhibits Pomc. Adenoviral delivery of constitutively nuclear or transactivation-deficient FoxO1 mutants to arcuate nucleus; promoter coactivator/corepressor exchange assays Nature medicine High 16604086
2019 NPY co-released from AgRP neurons is uniquely required for the long-lasting effects of AgRP neuron stimulation on feeding; deletion of NPY (but not AgRP peptide or GABA) from AgRP neurons abolished optogenetically-stimulated feeding, which was rescued by re-expression of NPY selectively in AgRP neurons. Conditional knockout of NPY, AgRP, or GABA in AgRP neurons; optogenetic stimulation; rescue by selective NPY re-expression eLife High 31033437
2011 GABAergic output from AgRP neurons to the parabrachial nucleus (PBN) is necessary to prevent anorexia; chronic delivery of a GABA-A receptor partial agonist (bretazenil) into the PBN rescues feeding and body weight after acute AgRP neuron ablation, whereas melanocortin 4 receptor blockade is insufficient. Diphtheria toxin ablation of AgRP neurons; chronic pharmacological GABA-A agonist delivery to PBN; pharmacological MC4R blockade European journal of pharmacology High 21211531
2016 Fasting increases AMPK activity specifically in AgRP neurons; increased AMPK activity in AgRP neurons is both necessary and sufficient for fasting-induced spinogenesis and increased excitatory synaptic activity; the AMPK phosphorylation target mediating this synaptic plasticity is p21-activated kinase (PAK). Neuron-specific AMPK activity measurement and manipulation; dendritic spine counting; electrophysiology in AgRP neurons Neuron High 27321921
2003 Zebrafish AGRP is expressed exclusively in the hypothalamus, and fasting significantly upregulates AGRP transcript levels without altering POMC levels, demonstrating that metabolic-state regulation of AGRP is evolutionarily conserved in vertebrates. Cloning of zebrafish AGRP cDNA; in situ hybridization; RT-PCR under fasting conditions Endocrine Medium 14709799
2004 A 42.5-kb region upstream of the Agrp transcription unit, containing three evolutionarily conserved regions between mouse and human, is necessary and sufficient for arcuate nucleus-specific and fasting-responsive Agrp expression in transgenic mice. BAC reporter transgenic mice with varying amounts of upstream sequence; reporter expression analysis; fasting challenge Endocrinology High 15345681
2017 AgRP is expressed in adrenal medullary chromaffin cells that also synthesize catecholamines and NPY; short-term fasting increases adrenal AgRP expression; AgRP antagonizes presynaptic MC3/4 receptors on preganglionic neurons to modulate sympathetic input strength, but does not alter optogenetically evoked catecholamine release from isolated chromaffin cells. Immunohistochemistry, flow cytometry, RT-PCR in adrenal gland; electrophysiology (paired-pulse ratio); optogenetic catecholamine release assay Endocrinology Medium 28531318
2017 AgRP (chicken) functions as an inverse agonist at cMC3R and cMC4R constitutive activity and as an antagonist of ACTH/α-MSH action at both receptors, as demonstrated in CHO cells using luciferase reporter assays; MRAP2 co-expression modulates constitutive activity and ligand sensitivity of both receptors, with physical interaction confirmed by co-immunoprecipitation. CHO cell transfection; pGL3-CRE-luciferase reporter assay; dual-luciferase assay; co-immunoprecipitation The Journal of endocrinology Medium 28512117
2019 Activation of hypothalamic AgRP neurons rapidly alters whole-body substrate utilization, increasing carbohydrate utilization and decreasing fat utilization independent of caloric intake; these effects are coupled to increased lipogenesis, and inhibition of fatty acid synthase blunts the metabolic effects of AgRP neuron activation. Optogenetic/chemogenetic activation of AgRP neurons; indirect calorimetry; fatty acid synthase inhibitor treatment; pair-feeding Nature communications High 30659173
2022 TET3, a DNA dioxygenase, epigenetically controls AgRP expression in AGRP neurons; CRISPR-mediated Tet3 ablation in AGRP neurons activates these neurons, upregulates Agrp, Npy, and the vesicular GABA transporter Slc32a1, and impedes leptin signaling. TET3 dynamically associates with the Agrp promoter in response to leptin, inducing 5-hydroxymethylcytosine modification associated with a chromatin-modifying complex that inhibits Agrp transcription. CRISPR-mediated conditional Tet3 knockout in AGRP neurons; chromatin immunoprecipitation; 5hmC modification assay; gene expression profiling The Journal of clinical investigation High 36189793
2023 Fasting-induced liver autophagy is regulated by hypothalamic AgRP neurons via NPY release in the paraventricular nucleus (PVH), where NPY acts on NPY1R-expressing neurons to activate PVHCRH neurons; AgRP neuron activation increases circulating corticosterone, and hepatic glucocorticoid receptor is required for AgRP neuron-dependent activation of hepatic autophagy. Optogenetic and chemogenetic AgRP neuron manipulation; PVH-specific viral injections; glucocorticoid receptor knockdown; autophagy assays; phosphorylation profiling Cell metabolism High 37075752
2019 DNA methyltransferase Dnmt3a in AgRP neurons is required for normal epigenetic development and neuron-specific gene expression; deletion of Dnmt3a in AgRP neurons causes sedentary phenotype, reduced voluntary exercise, and increased adiposity, associated with promoter hypomethylation and increased expression of Bmp7 in AgRP neurons. Conditional Dnmt3a knockout in AgRP neurons; whole-genome bisulfite sequencing; transcriptional profiling of arcuate neuronal nuclei Nature communications High 31792207
2015 FOXO1 in AgRP neurons controls food intake and glucose homeostasis via the downstream effector Gpr17; AgRP neuron-specific Gpr17 knockout mice phenocopy FOXO1 knockouts (reduced food intake, leanness, increased insulin and leptin sensitivity), positioning Gpr17 as an effector of FOXO1 orexigenic signaling in AgRP neurons. AgRP neuron-specific Gpr17 conditional knockout; metabolic phenotyping; insulin and leptin sensitivity assays Diabetes Medium 26180086
2023 CaMK1D is activated in AgRP/NPY neurons by ghrelin and mediates ghrelin-dependent food intake; CaMK1D deletion in AgRP/NPY (but not POMC) neurons confers resistance to ghrelin, reduces body weight, and protects against diet-induced obesity; mechanistically, CaMK1D loss attenuates CREB phosphorylation and CREB-dependent AgRP/NPY neuropeptide expression in projections to the PVN. Global and AgRP-specific Camk1d conditional knockout; ghrelin administration; CREB phosphorylation assay; neuropeptide expression in PVN fiber projections Nature metabolism High 37277610
2023 Asprosin activates AgRP neurons via binding to Ptprd (protein tyrosine phosphatase receptor δ); intracellularly, this activates small-conductance calcium-activated potassium (SK3) channels, with the SK3 current increasing upon asprosin deficiency and decreasing upon elevated asprosin. AgRP-specific SK3 deletion blocks asprosin-induced AgRP activation and hyperphagia; Ptprd knockout abolishes asprosin's effects on SK current and AgRP neuronal activity. AgRP-specific SK3 knockout; Ptprd knockout; patch-clamp electrophysiology measuring SK current; chemogenetic feeding assays Science advances High 36812308
2018 Dlx1/2 transcription factors repress AgRP neuronal identity by directly binding and repressing expression of Otp, a transcription factor required for AgRP neuron generation; Dlx1/2-deficient mice show loss of GHRH neurons and an increase in AgRP neurons, while Otp is required for AgRP neuron generation. Conditional Dlx1/2 knockout; Otp loss-of-function; chromatin binding assays; neuron counting and metabolic phenotyping Nature communications High 29795232
2020 AgRP neurons inhibit lateral hypothalamic orexin neurons via GABA, forming an inhibitory AgRP→orexin circuit; chemogenetic suppression of AgRP neurons increases innate avoidance behavior in an orexin receptor-dependent manner, and optogenetic evidence directly demonstrates GABAergic connectivity. Optogenetic identification of AgRP→orexin circuit; chemogenetic AgRP suppression; orexin receptor antagonism; calcium imaging of orexin neurons The Journal of physiology Medium 32667686
2017 Agrp neuron electrical and biochemical hyperactivity induced by dietary doses of ethanol in brain slices is required for ethanol-induced overeating in vivo; chemogenetic suppression of Agrp neurons in single-housed mice prevents ethanol-induced overconsumption. Ex vivo electrophysiology; chemogenetic circuit-specific interference in vivo; ethanol feeding assay Nature communications Medium 28072397
2022 NPY originating specifically from AgRP neurons controls feeding via NPY1R (mediating increased food intake and respiratory quotient) and controls energy expenditure and locomotion via NPY2R, as demonstrated by conditional Npy deletion in AgRP neurons with selective receptor ligand rescue experiments. Conditional AgRP-neuron-specific Npy knockout; DREADD activation; selective NPY1R and NPY2R ligand rescue; metabolic phenotyping Molecular metabolism High 35167990
2023 MC3R expression within AgRP neurons is required for normal activation of AgRP neurons in response to fasting, cold exposure, or ghrelin; conditional MC3R knockout in AgRP neurons abolishes these activations while leaving inhibitory responses (food detection) intact, demonstrating MC3R acts cell-autonomously at the AgRP soma to relay hormonal and neuronal energy-need signals. Conditional MC3R knockout in AgRP neurons; calcium imaging of AgRP neurons in response to fasting, cold, and ghrelin Cell reports High 37792535
2020 Central α-klotho suppresses NPY/AgRP neuron activity at least in part by enhancing miniature inhibitory postsynaptic currents; this effect is mediated through FGFR1 signaling and PI3K, and mechanistically involves phosphorylation of AKT, ERK, and FOXO1 with consequent blunting of AgRP gene transcription. Intracerebroventricular α-klotho administration; patch clamp electrophysiology; FGFR1 and PI3K inhibition; western blot for signaling intermediates; qPCR for AgRP Diabetes Medium 32332158
2017 Heparin increases food intake and AgRP release by stimulating AgRP neurons; mechanistically, heparin competes with insulin for insulin receptor binding on AgRP neurons, thereby inhibiting FoxO1 activity to promote AgRP release. Electrophysiology; pharmacology; molecular biology; chemogenetic approaches; competitive binding assay for insulin receptor Cell reports Medium 28877477
2023 Daily AgRP neuron activity follows the circadian rest-activity cycle via a process requiring an intact suprachiasmatic nucleus (SCN) and synchronization by light, rather than acting primarily as a food-deprivation counter; imposing novel feeding patterns resynchronizes AgRP neuron activity rhythm and drives anticipatory behavior through DMHPDYN neurons. In vivo neuron dynamics measurements; timed optogenetic activation; SCN lesion; light-cycle manipulation; photostimulation of DMHPDYN neurons Nature neuroscience High 37957320
2019 AGRP neurons modulate fasting-induced anxiolytic effects; chemogenetic activation of AgRP neurons reduces anxiety in fed mice, while chemogenetic inactivation reduces fasting-induced anxiolysis, establishing that AgRP neuron activity is necessary and sufficient for the anxiolytic component of fasting. DREADD-based chemogenetic activation and inhibition in AgRP-Cre mice; open field and elevated plus-maze behavioral tests Translational psychiatry Medium 30850579
2022 Food-induced dopamine release in the arcuate nucleus acts via dopamine receptor D1 (Drd1) expressed in AgRP/NPY neurons to promote feeding; Drd1 deletion in AgRP/NPY neurons attenuates foraging and refeeding of high-fat diet, while stimulation of Drd1+AgRP/NPY co-expressing neurons induces voracious feeding. AgRP/NPY-specific Drd1 conditional knockout; chemogenetic stimulation of Drd1+AgRP/NPY neurons; in vivo dopamine release measurement in ARC; feeding assays Cell reports Medium 36450244
2021 Cold-responsive neurons in the medial preoptic area (mPOA) make excitatory synapses onto ARCAgRP neurons; inhibition of either ARCAgRP neurons or ARC-projecting mPOA neurons attenuates cold-evoked feeding, while activation of the mPOA-to-ARC projection increases food intake, defining an mPOA→ARCAgRP neural pathway for cold-evoked feeding. Calcium imaging of AgRP neurons during cold exposure; optogenetic pathway activation/inhibition; synaptic tracing Cell reports Medium 34380037
2015 AgRP neurons regulate bone mass; impairment of AgRP neuronal function (via Ucp2 deletion, early postnatal neuron ablation, or Sirt1 deletion in AgRP neurons) causes osteopenia; this effect is independent of leptin receptor signaling in AgRP neurons and is mediated by suppression of sympathetic tone, as reversal of sympathetic suppression rescues osteopenia in AgRP-Sirt1 KO mice. Multiple mouse lines with AgRP neuron-specific genetic manipulations; quantitative bone density measurements; sympathetic tone modulation Cell reports Medium 26411686
2023 The mouse Agrp gene has three distinct promoter/enhancer regions directing transcription of separate Agrp transcripts; one region (Agrp-B) is regulated by bile acids. AGRP-B-expressing cells are located in pituitary pars tuberalis endocrine cells and folliculostellate cells, co-express diacylglycerol lipase B, and are distinct from hypothalamic AgRP neurons. Chemogenetic inhibition of AGRP-B cells improves glucose tolerance by enhancing glucose-stimulated insulin secretion. Agrp-B knockin FLP/knockout allele; immunohistochemistry; DREADD-mediated chemogenetic inhibition; glucose tolerance and insulin secretion assays The Journal of clinical investigation Medium 36787185
2023 Hypothalamic AgRP neurons exert immunoregulatory control over systemic TNF-α release during endotoxemia; chemogenetic activation of AgRP neurons reduces acute TNF-α release, and this effect requires glucocorticoid receptor expression in AgRP neurons; glucocorticoid receptor deletion from AgRP neurons prevents endotoxemia-induced neuronal desensitization and counteracts fasting-induced TNF-α suppression. Chemogenetic AgRP neuron activation; AgRP-neuron-specific glucocorticoid receptor deletion; cytokine measurement; LPS endotoxemia model Current biology Medium 36182699
2024 Iron overload in AgRP neurons (mediated by transferrin receptor 1, Tfrc) promotes obesity by increasing AgRP neuron activity; mechanistically, iron overload activates oxidative stress, endoplasmic reticulum stress, NF-κB signaling, and SOCS3 expression, impairing insulin and leptin sensitivity in AgRP neurons. AgRP-specific Tfrc conditional knockout and overexpression; central deferoxamine treatment; electrophysiology; western blot for ER stress and NF-κB markers; insulin/leptin sensitivity assays Cell reports Medium 38460132
2017 PDK1-FoxO1 signaling in AgRP neurons controls bone metabolism via the GHRH-GH-IGF-1 axis; AgRP-neuron-specific PDK1 knockout reduces bone mineral density, stature, plasma GH and IGF-1, and GHRH mRNA, and these defects are rescued by expression of a transactivation-defective FoxO1 (Δ256) in the same neurons. AgRP-neuron-specific PDK1 conditional knockout; AgRP-PDK1-FoxO1 double transgenic rescue; QCT bone density; plasma GH/IGF-1 measurement; qPCR for GHRH Molecular metabolism Medium 28462077
2012 Phylogenetic analysis identifies AgRP as the most distantly related member of the Agouti-like peptide family, splitting from a common ancestor before ASIP and A2 diverged; A2 sequences (including ASIP2/AgRP2) reside in a chromosomal region syntenic with Hsa 8, and novel Agouti-like homologues with the C-x(6)-C-C motif were identified in arthropods and fungi. Comprehensive vertebrate sequence mining; phylogenetic analysis; sinusoidal Hough transform synteny analysis PloS one Low 22815886
2024 miR-33 expressed in AgRP neurons controls multiple bioenergetic processes including mitochondrial biogenesis and fatty acid metabolism; loss of miR-33 leads to increased feeding and obesity, with identified miR-33 target genes in these pathways serving as regulatory nodes for AgRP neuron activation. AgRP-neuron-specific miR-33 conditional knockout mouse model; metabolic phenotyping; miR-33 target gene profiling Nature communications Medium 38459068
2019 Insulin receptor signaling in AgRP neurons is required for hepatic insulin action: mice lacking insulin receptor in AgRP neurons (AgRP IR KO) exhibit impaired ability of insulin to suppress hepatic glucose production, but unaltered adipose tissue lipolysis regulation. AgRP-neuron-specific insulin receptor conditional knockout; hyperinsulinemic-euglycemic clamps; hepatic glucose production assay; lipolysis assay Diabetes Medium 28385803
2023 Microglia regulate postnatal development of AgRP neurons by engulfing perineuronal net (PNN) components surrounding AgRP neurons; microglial depletion during a critical postnatal period increases AgRP neuron number and fiber density, enhances leptin sensitivity in the ARC, and increases neonatal feeding, identifying PNN plasticity as the mechanistic link. Microglial depletion in neonatal mice; immunofluorescence for PNN components; ex vivo engulfment assay; AgRP neuron counting; leptin sensitivity assay Molecular psychiatry Medium 38001338

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. The Journal of clinical investigation 1279 21364278
1998 DNA chips: state-of-the art. Nature biotechnology 484 9447591
2007 Human biomonitoring: state of the art. International journal of hygiene and environmental health 460 17376741
2006 Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake. Nature medicine 361 16604086
2012 Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO reports 324 23146889
2003 Sperm preparation for ART. Reproductive biology and endocrinology : RB&E 318 14617368
2011 DNA origami: the art of folding DNA. Angewandte Chemie (International ed. in English) 231 22162047
2018 Therapeutic Oligonucleotides: State of the Art. Annual review of pharmacology and toxicology 230 30285540
1999 Thymoma: state of the art. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 227 10561285
2009 Hormone and glucose signalling in POMC and AgRP neurons. The Journal of physiology 198 19770186
2001 The NPY/AgRP neuron and energy homeostasis. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 169 11840217
2021 Treatments for NAFLD: State of Art. International journal of molecular sciences 167 33652942
2007 Mastocytosis: state of the art. Pathobiology : journal of immunopathology, molecular and cellular biology 153 17587883
2019 Association of four imprinting disorders and ART. Clinical epigenetics 116 30732658
2019 Sustained NPY signaling enables AgRP neurons to drive feeding. eLife 108 31033437
2011 GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin-independent mechanism. European journal of pharmacology 105 21211531
2003 Agouti-related protein (AGRP) is conserved and regulated by metabolic state in the zebrafish, Danio rerio. Endocrine 105 14709799
1998 Chromosome painting: a useful art. Human molecular genetics 95 9735383
2002 Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice. American journal of physiology. Regulatory, integrative and comparative physiology 94 12376393
2010 Herpesviruses and immunity: the art of evasion. Veterinary microbiology 90 20303681
2019 Regulation of substrate utilization and adiposity by Agrp neurons. Nature communications 88 30659173
2017 Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action. Diabetes 87 28385803
2010 MDC1: The art of keeping things in focus. Chromosoma 79 20224865
2016 A Postsynaptic AMPK→p21-Activated Kinase Pathway Drives Fasting-Induced Synaptic Plasticity in AgRP Neurons. Neuron 75 27321921
2018 Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise. Molecular metabolism 74 30292523
2021 State-of-the-Art Biocatalysis. ACS central science 73 34345663
2013 Allopregnanolone: state of the art. Progress in neurobiology 73 24121112
2013 Red cell investigations: art and artefacts. Blood reviews 71 23425684
2005 The art of arteriogenesis. Cell biochemistry and biophysics 71 16043879
2019 Earliest hunting scene in prehistoric art. Nature 66 31827284
2017 Ongoing HIV Replication During ART Reconsidered. Open forum infectious diseases 62 30310821
2019 Seeds and the Art of Genome Maintenance. Frontiers in plant science 61 31214224
2023 Nutrient-sensing AgRP neurons relay control of liver autophagy during energy deprivation. Cell metabolism 58 37075752
2023 Agrp-negative arcuate NPY neurons drive feeding under positive energy balance via altering leptin responsiveness in POMC neurons. Cell metabolism 57 37201523
2014 Imprinting methylation errors in ART. Reproductive medicine and biology 57 25298744
2014 MYC and the art of microRNA maintenance. Cold Spring Harbor perspectives in medicine 53 24737842
2012 The neuroendocrine circuitry controlled by POMC, MSH, and AGRP. Handbook of experimental pharmacology 52 22249810
2017 The interaction of MC3R and MC4R with MRAP2, ACTH, α-MSH and AgRP in chickens. The Journal of endocrinology 48 28512117
2018 Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons. Nature communications 47 29795232
2015 Gpr17 in AgRP Neurons Regulates Feeding and Sensitivity to Insulin and Leptin. Diabetes 45 26180086
2023 AgRP neurons are not indispensable for body weight maintenance in adult mice. Cell reports 44 37422762
2019 AGRP neurons modulate fasting-induced anxiolytic effects. Translational psychiatry 44 30850579
2006 AgRP in energy balance: Will the real AgRP please stand up? Cell metabolism 43 16459309
2015 AgRP Neurons Regulate Bone Mass. Cell reports 41 26411686
2012 microRNAs: the art of silencing in the ear. EMBO molecular medicine 40 22745034
2023 AgRP neurons encode circadian feeding time. Nature neuroscience 39 37957320
2021 An mPOA-ARCAgRP pathway modulates cold-evoked eating behavior. Cell reports 39 34380037
2006 Polymorphisms in the NPY and AGRP genes and body fatness in Dutch adults. International journal of obesity (2005) 38 16568137
2004 Transcriptional regulation of agouti-related protein (Agrp) in transgenic mice. Endocrinology 35 15345681
2015 Geminiviruses for biotechnology: the art of parasite taming. The New phytologist 33 26214399
2019 DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice. Nature communications 32 31792207
2022 NPY derived from AGRP neurons controls feeding via Y1 and energy expenditure and food foraging behaviour via Y2 signalling. Molecular metabolism 29 35167990
2020 The Art of Mast Cell Adhesion. Cells 29 33322506
2021 Representations of uncertainty: where art thou? Current opinion in behavioral sciences 27 34026948
2018 Control of Energy Expenditure by AgRP Neurons of the Arcuate Nucleus: Neurocircuitry, Signaling Pathways, and Angiotensin. Current hypertension reports 27 29556733
2024 LncRNAs: the art of being influential without protein. Trends in plant science 26 38368122
2017 Agrp neuron activity is required for alcohol-induced overeating. Nature communications 26 28072397
2023 Asprosin promotes feeding through SK channel-dependent activation of AgRP neurons. Science advances 25 36812308
2022 Food-induced dopamine signaling in AgRP neurons promotes feeding. Cell reports 25 36450244
2017 AgRP-Expressing Adrenal Chromaffin Cells Are Involved in the Sympathetic Response to Fasting. Endocrinology 25 28531318
2016 Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice. Endocrinology 25 27111742
2022 State-of-the-art therapies for Rett syndrome. Developmental medicine and child neurology 24 36056801
2015 The Art of Intraoperative Glioma Identification. Frontiers in oncology 24 26284196
2007 Hypothalamic and hindbrain NPY, AGRP and NE increase consummatory feeding responses. Physiology & behavior 24 17289093
1977 Art and recovery style from psychosis. The Journal of nervous and mental disease 24 320289
2020 Orexin neurons and inhibitory Agrp→orexin circuits guide spatial exploration in mice. The Journal of physiology 23 32667686
2024 Iron overload in hypothalamic AgRP neurons contributes to obesity and related metabolic disorders. Cell reports 22 38460132
2023 CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake. Nature metabolism 22 37277610
2022 TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons. The Journal of clinical investigation 22 36189793
2024 microRNA-33 controls hunger signaling in hypothalamic AgRP neurons. Nature communications 21 38459068
2020 Central α-Klotho Suppresses NPY/AgRP Neuron Activity and Regulates Metabolism in Mice. Diabetes 21 32332158
2015 Review: Influence of ART on HIV genetics. Current opinion in HIV and AIDS 21 25389802
2015 The art of magnesium transport. Magnesium research 21 26446763
2014 Centrosomes and the art of mitotic spindle maintenance. International review of cell and molecular biology 21 25376493
2002 Preservation of fertility in nature and ART. Reproduction (Cambridge, England) 21 11869181
2023 Microglia shape AgRP neuron postnatal development via regulating perineuronal net plasticity. Molecular psychiatry 20 38001338
2018 Targeting AgRP neurons to maintain energy balance: Lessons from animal models. Biochemical pharmacology 20 30012460
2019 JAK2/STAT3 Pathway is Required for α7nAChR-Dependent Expression of POMC and AGRP Neuropeptides in Male Mice. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 19 31592599
2017 Heparin Increases Food Intake through AgRP Neurons. Cell reports 19 28877477
2005 Expression of AgRP, NPY, POMC and CART in human fetal and adult hippocampus. Neuropeptides 19 15885775
2024 Sucrose overconsumption impairs AgRP neuron dynamics and promotes palatable food intake. Cell reports 18 38224492
2017 PDK1-FoxO1 pathway in AgRP neurons of arcuate nucleus promotes bone formation via GHRH-GH-IGF1 axis. Molecular metabolism 18 28462077
2002 Safeguarding ART. Nature cell biology 18 12479610
2023 Growth hormone receptor (GHR) in AgRP neurons regulates thermogenesis in a sex-specific manner. GeroScience 17 36633824
2013 Identification and preparation of sperm for ART. The Urologic clinics of North America 17 24286775
2023 Pseudogenes in Cancer: State of the Art. Cancers 16 37627052
2016 Nano-ART and NeuroAIDS. Drug delivery and translational research 16 27137528
2015 Art on the Nanoscale and Beyond. Advanced materials (Deerfield Beach, Fla.) 16 26671704
2012 Identification of distant Agouti-like sequences and re-evaluation of the evolutionary history of the Agouti-related peptide (AgRP). PloS one 16 22815886
2023 Melanocortin-3 receptor expression in AgRP neurons is required for normal activation of the neurons in response to energy deficiency. Cell reports 15 37792535
2017 Mechanisms for AgRP neuron-mediated regulation of appetitive behaviors in rodents. Physiology & behavior 15 29031550
2024 BCAAs acutely drive glucose dysregulation and insulin resistance: role of AgRP neurons. Nutrition & diabetes 14 38844453
2022 Signaling peptides direct the art of rebirth. Trends in plant science 14 35397996
2000 Appearance, cosmetics, and body art in adolescents. Dermatologic clinics 14 11059375
2023 CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst. Biology of sex differences 13 36966335
2022 AgRP neurons control structure and function of the medial prefrontal cortex. Molecular psychiatry 13 35906488
2022 Hypothalamic AgRP neurons exert top-down control on systemic TNF-α release during endotoxemia. Current biology : CB 13 36182699
2019 Relationship of α-MSH and AgRP axons to the perikarya of melanocortin-4 receptor neurons. Brain research 13 31009611
2023 The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis. The Journal of clinical investigation 12 36787185
1996 Enzymes in mineralizing systems: state of the art. Connective tissue research 12 9084656

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