2025
Endoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior
Jin S, Yoon N, Wei M, Worgall T, Rubinelli L, Horvath T, Min W, Diano N, di Lorenzo A, Diano S. Endoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior. Cell Metabolism 2025, 37: 1400-1412.e8. PMID: 40334659, PMCID: PMC12136989, DOI: 10.1016/j.cmet.2025.04.005.Peer-Reviewed Original ResearchConceptsAgRP neuron activityNogo-AAgRP neuronsNeuronal activityCeramide levelsNogo-A expressionCellular lipid metabolismIntracellular lipid transportSphingolipid de novo biosynthesisDownregulation of enzymesIncreased ceramide levelsLipid metabolismHigh-fat diet-induced obesityFeeding behaviorAgouti-related proteinControl of feedingControlling lipid metabolismAssociated with brain developmentWhole-body metabolismFatty acid oxidationReticulon 4Food intakeMitochondrial functionSynaptic plasticityLipid transport
2024
NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation
Dodt S, Widdershooven N, Dreisow M, Weiher L, Steuernagel L, Wunderlich F, Brüning J, Fenselau H. NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation. Nature Communications 2024, 15: 5439. PMID: 38937485, PMCID: PMC11211344, DOI: 10.1038/s41467-024-49766-0.Peer-Reviewed Original ResearchConceptsBed nucleus of the stria terminalisNPY-deficient miceBed nucleus of the stria terminalis neuronsGABAergic inputsControl of feeding behaviorPromote feedingAgRP neuronsOrexigenic neuropeptide Y (NPYSuppress food intakeNeuropeptide Y (NPYAmygdala circuitsAnxiety signalsExtended amygdalaCentral amygdalaBed nucleusCeA projectionsStria terminalisSynaptic adaptationDecreased anxietyAmygdalaSynaptic plasticityRelevant circuitsDecreased feedingAnxietyHypothalamic neuronsmicroRNA-33 controls hunger signaling in hypothalamic AgRP neurons
Price N, Fernández-Tussy P, Varela L, Cardelo M, Shanabrough M, Aryal B, de Cabo R, Suárez Y, Horvath T, Fernández-Hernando C. microRNA-33 controls hunger signaling in hypothalamic AgRP neurons. Nature Communications 2024, 15: 2131. PMID: 38459068, PMCID: PMC10923783, DOI: 10.1038/s41467-024-46427-0.Peer-Reviewed Original ResearchConceptsAgRP neuronsFeeding behaviorFatty acid metabolismNon-coding RNAsMitochondrial biogenesisRegulatory pathwaysTarget genesHypothalamic AgRP neuronsExcessive nutrient intakeCentral regulatorBioenergetic processesAcid metabolismActivation of AgRP neuronsModulate feeding behaviorCentral regulation of feeding behaviorRegulation of feeding behaviorMiR-33Hunger signalsMicroRNA-33Metabolic diseasesAlternative therapeutic approachLoss of miR-33Mouse modelMetabolic dysfunctionRegulationReciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism
De Solis A, Del Río-Martín A, Radermacher J, Chen W, Steuernagel L, Bauder C, Eggersmann F, Morgan D, Cremer A, Sué M, Germer M, Kukat C, Vollmar S, Backes H, Rahmouni K, Kloppenburg P, Brüning J. Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism. Nature Metabolism 2024, 6: 473-493. PMID: 38378998, PMCID: PMC10963273, DOI: 10.1038/s42255-024-00987-z.Peer-Reviewed Original ResearchInhibition of POMC neuronsPOMC neuronsFood intakeAgRP neuronsEffects of Agrp neuron activationActivation of AgRP neuronsActivating AgRP neuronsActivation of AgRPInhibit POMC neuronsProopiomelanocortin (POMC)-expressing neuronsAgRP neuron activityNucleus tractus solitariiRegulate food intakePromote food consumptionSystemic insulin sensitivityControl of feedingParaventricular nucleusTractus solitariiNeuronal inhibitionTH+ neuronsFemale miceChemogenetic receptorsNeuronal activityAgRPInsulin sensitivity
2023
A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model
Lv H, Catarino J, Li D, Liu B, Gao X, Horvath T, Huang Y. A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300015120. PMID: 37036983, PMCID: PMC10120042, DOI: 10.1073/pnas.2300015120.Peer-Reviewed Original ResearchConceptsVesicular GABA transporterActivity-based anorexiaExpression of AgRPNeuropeptide YAgRP neuronsAnorexia nervosaAnxiety/depressive-like behaviorsHypothalamic AgRP neuronsDepressive-like behaviorCurrent treatment optionsHigh relapse rateStress-related disordersHuman neuronal cellsNutritional supportRelapse rateTreatment optionsAnxiolytic effectsPsychiatric illnessMouse modelAnimal modelsHigh mortalityGABA transporterGenetic ablationNeuronal cellsNeurons
2022
TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons
Xie D, Stutz B, Li F, Chen F, Lv H, Sestan-Pesa M, Catarino J, Gu J, Zhao H, Stoddard CE, Carmichael GG, Shanabrough M, Taylor HS, Liu ZW, Gao XB, Horvath TL, Huang Y. TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons. Journal Of Clinical Investigation 2022, 132: e162365. PMID: 36189793, PMCID: PMC9525119, DOI: 10.1172/jci162365.Peer-Reviewed Original ResearchConceptsAgRP neuronsNeuropeptide YExpression of AgRPControl of feedingHypothalamic agoutiAnxiolytic effectsNeurotransmitter GABAMouse modelLeptin signalingStress-like behaviorsGenetic ablationNeuronsAgRPCritical central regulatorsEnergy expenditureGABAEnergy metabolismAppetiteFeedingCentral regulatorMetabolismCentral controlHuman cellsTET3ObesityAgRP neurons control structure and function of the medial prefrontal cortex
Stutz B, Waterson MJ, Šestan-Peša M, Dietrich MO, Škarica M, Sestan N, Racz B, Magyar A, Sotonyi P, Liu ZW, Gao XB, Matyas F, Stoiljkovic M, Horvath TL. AgRP neurons control structure and function of the medial prefrontal cortex. Molecular Psychiatry 2022, 27: 3951-3960. PMID: 35906488, PMCID: PMC9891653, DOI: 10.1038/s41380-022-01691-8.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAgRP neuronsNon-selective dopamine receptor antagonistBrain functionPrefrontal cortexHypothalamic AgRP neuronsMedial thalamic neuronsAdministration of clozapineDopamine receptor antagonistVentral tegmental areaOscillatory network activityHigher-order brain functionsHypothalamic agoutiThalamic neuronsChemogenetic inhibitionDopaminergic neuronsReceptor antagonistTegmental areaNeuronal pathwaysSensorimotor gatingAdult miceModulatory impactAmbulatory behaviorConstitutive impairmentNeuronsAgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids
Endle H, Horta G, Stutz B, Muthuraman M, Tegeder I, Schreiber Y, Snodgrass IF, Gurke R, Liu ZW, Sestan-Pesa M, Radyushkin K, Streu N, Fan W, Baumgart J, Li Y, Kloss F, Groppa S, Opel N, Dannlowski U, Grabe HJ, Zipp F, Rácz B, Horvath TL, Nitsch R, Vogt J. AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids. Nature Metabolism 2022, 4: 683-692. PMID: 35760867, PMCID: PMC9940119, DOI: 10.1038/s42255-022-00589-7.Peer-Reviewed Original ResearchConceptsFasting-induced hyperphagiaCortical excitabilityAgRP neuronsLysophosphatidic acidPeripheral metabolismHigher Body Mass IndexFasting-induced elevationHypothalamic AgRP neuronsEffects of LPABody mass indexHigher cortical excitabilityBrain lipid levelsCentral nervous systemPrevalence of typeGlutamatergic transmissionHypothalamic agoutiMass indexOvernight fastingPeptide neuronsCortical synapsesLipid levelsFood intakeCerebrospinal fluidNervous systemPhospholipid levelsDevelopment of “Hunger Neurons” and the Unanticipated Relationship Between Energy Metabolism and Mother-Infant Interactions
Iyilikci O, Zimmer MR, Dietrich MO. Development of “Hunger Neurons” and the Unanticipated Relationship Between Energy Metabolism and Mother-Infant Interactions. Biological Psychiatry 2022, 91: 907-914. PMID: 35397878, PMCID: PMC10184517, DOI: 10.1016/j.biopsych.2022.02.962.Peer-Reviewed Original Research
2021
Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice
Varela L, Stutz B, Song JE, Kim JG, Liu ZW, Gao XB, Horvath TL. Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice. Journal Of Clinical Investigation 2021, 131 PMID: 33848272, PMCID: PMC8121506, DOI: 10.1172/jci144239.Peer-Reviewed Original ResearchConceptsAgRP neuronsHypothalamic feeding circuitsInhibitory neurotransmitter GABAGhrelin administrationInhibitory toneAstrocytic responseMetabolic milieuProstaglandin E2Neurotransmitter GABANeuronal controlSynaptic plasticityGlial processesNeuronsNeural excitationMitochondrial adaptationsFood deprivationAstrocytesPerikaryaFeeding circuitRegion crucialFeedingObesityGABAExcitabilityChemogeneticsDrp1 is required for AgRP neuronal activity and feeding
Jin S, Yoon NA, Liu ZW, Song JE, Horvath TL, Kim JD, Diano S. Drp1 is required for AgRP neuronal activity and feeding. ELife 2021, 10: e64351. PMID: 33689681, PMCID: PMC7946429, DOI: 10.7554/elife.64351.Peer-Reviewed Original ResearchConceptsAgRP neuronal activityFatty acid oxidationAgRP neuronsNeuronal activityAgRP neuronal functionHypothalamic AgRP neuronsBody weight regulationMitochondrial fatty acid utilizationWhole-body energy homeostasisHypothalamic orexigenic agoutiFatty acid utilizationAcid oxidationFat massCKO miceNeuronal activationPeptide-1Body weightNeuronal functionOrexigenic agoutiEnergy homeostasisMitochondrial fissionSignificant decreaseEnergy expenditureNeuronsAcid utilizationAuthor Correction: AgRP neurons control compulsive exercise and survival in an activity-based anorexia model
Miletta MC, Iyilikci O, Shanabrough M, Šestan-Peša M, Cammisa A, Zeiss CJ, Dietrich MO, Horvath TL. Author Correction: AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nature Metabolism 2021, 3: 288-288. PMID: 33495625, DOI: 10.1038/s42255-021-00351-5.Peer-Reviewed Original Research
2020
AgRP neurons control compulsive exercise and survival in an activity-based anorexia model
Miletta MC, Iyilikci O, Shanabrough M, Šestan-Peša M, Cammisa A, Zeiss CJ, Dietrich MO, Horvath TL. AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nature Metabolism 2020, 2: 1204-1211. PMID: 33106687, DOI: 10.1038/s42255-020-00300-8.Peer-Reviewed Original ResearchConceptsAgRP neuronsActivity-based anorexia modelAgRP neuronal activityVivo fiber photometryFood-restricted miceFood-restricted animalsCompulsive exerciseAnorexia modelHypothalamic agoutiNeuropeptide YExercise volumeFood intakeMouse modelNeuronal activityFiber photometryDaily activationNeuronal circuitsPsychiatric conditionsAnorexia nervosaChemogenetic toolsNeuronsLong-term behavioral impactElevated fat contentVoluntary cessationFat content
2019
1835-P: Deletion of Insulin Receptor Substrate 2 in AGRP Neurons Causes Beta-Cell Dysfunction
TAO R, COPPS K, WHITE M, STOEHR O. 1835-P: Deletion of Insulin Receptor Substrate 2 in AGRP Neurons Causes Beta-Cell Dysfunction. Diabetes 2019, 68 DOI: 10.2337/db19-1835-p.Peer-Reviewed Original ResearchAgRP neuronsArcuate nucleusInsulin resistanceInsulin secretionInsulin receptor substrateType 2 diabetes progressesCompensatory insulin secretionL-arginine treatmentBeta-cell compensationBeta-cell dysfunctionPeripheral insulin resistanceBeta-cell failureBeta-cell functionHigh-fat dietInsulin secretory functionType 2 diabetesSteady-state hyperglycemiaGlucose infusion rateΒ-cell dysfunctionInsulin receptor substrate 2Pancreatic β-cellsGrowth-promoting actionDiabetes progressesFat dietHyperglycemic clampFunctional Ontogeny of Hypothalamic Agrp Neurons in Neonatal Mouse Behaviors
Zimmer MR, Fonseca AHO, Iyilikci O, Pra RD, Dietrich MO. Functional Ontogeny of Hypothalamic Agrp Neurons in Neonatal Mouse Behaviors. Cell 2019, 178: 44-59.e7. PMID: 31104844, PMCID: PMC6688755, DOI: 10.1016/j.cell.2019.04.026.Peer-Reviewed Original ResearchConceptsHypothalamic AgRP neuronsAgRP neuronsAdult micePostnatal day 10 miceVivo fiber photometryFunctional ontogenyIsolation-induced ultrasonic vocalizationsNon-nutritive sucklingUltrasonic vocalizationsMilk ingestionFiber photometryMilk deprivationFood ingestionNeuronsMiceMouse behaviorIngestionNeonatesGABALittermatesOveractivationRegulation of substrate utilization and adiposity by Agrp neurons
Cavalcanti-de-Albuquerque JP, Bober J, Zimmer MR, Dietrich MO. Regulation of substrate utilization and adiposity by Agrp neurons. Nature Communications 2019, 10: 311. PMID: 30659173, PMCID: PMC6338802, DOI: 10.1038/s41467-018-08239-x.Peer-Reviewed Original ResearchConceptsFat mass accumulationAgRP neuronsPositive energy balanceWhole-body substrate utilizationAgRP neuron activationHypothalamic AgRP neuronsPair-feeding conditionsSubstrate utilizationFatty acid synthaseCaloric ingestionFat utilizationNeuronal mechanismsWeight gainNeuronsMetabolic changesMass accumulationKey enzymeAdiposityAcid synthaseEnergy metabolismNeuron activationLipogenesisActivationCarbohydrate utilizationMetabolic efficiencyActivation of Agrp neurons modulates memory-related cognitive processes in mice
Zimmer MR, Schmitz AE, Dietrich MO. Activation of Agrp neurons modulates memory-related cognitive processes in mice. Pharmacological Research 2019, 141: 303-309. PMID: 30610962, PMCID: PMC6400640, DOI: 10.1016/j.phrs.2018.12.024.Peer-Reviewed Original ResearchConceptsMemory-related cognitive processesCognitive processesMemory-related tasksBarnes maze taskBehavioral flexibilityAgRP neuronsSpontaneous alternation behaviorMaze taskSpatial learningY-maze testStereotyped behaviorAlternation behaviorFood intakeHypothalamic AgRP neuronsTaskNeuropeptide Y receptorsChemogenetic activationY receptorsMouse behaviorAdult miceMemoryNeuronsBehaviorLearningCritical regulator
2015
Mitochondria in Control of Hypothalamic Metabolic Circuits
Nasrallah C, Horvath T. Mitochondria in Control of Hypothalamic Metabolic Circuits. 2015, 186-202. DOI: 10.1002/9781119017127.ch8.Peer-Reviewed Original ResearchPOMC neuronsNutritional statusBody nutritional statusAgRP neuronsGhrelin increasesLeptin levelsFood intakeCentral regulationGlucose levelsMetabolic disordersNeuronal functionPrimary siteLipid metabolismMetabolic principlesMitochondrial dysfunctionNeuronsCessation of feedingBioenergetic adaptationImportant contributorMitochondrial dynamicsMetabolic circuitsHypothalamusDysfunctionSatietyIntakeAgRP Neurons Regulate Bone Mass
Kim JG, Sun BH, Dietrich MO, Koch M, Yao GQ, Diano S, Insogna K, Horvath TL. AgRP Neurons Regulate Bone Mass. Cell Reports 2015, 13: 8-14. PMID: 26411686, PMCID: PMC5868421, DOI: 10.1016/j.celrep.2015.08.070.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusBone DensityBone Diseases, MetabolicFemurGene Expression RegulationHomeostasisHypothalamusIon ChannelsLeptinMaleMiceMice, KnockoutMitochondrial ProteinsNeuronsNorepinephrinePhenotypePropranololReceptors, Adrenergic, betaReceptors, LeptinSignal TransductionSirtuin 1TibiaUncoupling Protein 2ConceptsAgRP neuronsCell-autonomous deletionSignificant regulatory roleAgRP neuronal functionBone massLeptin receptor deletionSkeletal bone metabolismTransgenic animalsRegulatory roleGene deletionBone homeostasisDeletionNeuronal functionPostnatal deletionSympathetic toneReceptor deletionArcuate nucleusLeptin actionBone metabolismSkeletal metabolismMultiple linesNeuronsMiceMetabolismCircuit integrityThe role of the hypothalamus in the maintenance of energy balance and peripheral glucose control
Varela L, Horvath T. The role of the hypothalamus in the maintenance of energy balance and peripheral glucose control. 2015, 529-537. DOI: 10.1002/9781118387658.ch36.Peer-Reviewed Original ResearchEnergy homeostasisPrevalence of obesityAnorectic hormonesAgRP neuronsHypothalamic POMCObese patientsGlucose controlGlucose homeostasisBody weightInsulin actionHormonal actionLeptinMajor targetInsulinHormoneBrainHomeostasisLatest findingsEnergy balanceSteady riseObesityPatientsHypothalamusPathwayPrevalence
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