2024
microRNA-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 dysfunctionRegulation
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 ResearchMeSH KeywordsAgouti-Related ProteinAnimalsAnorexia NervosaDioxygenasesHumansHypothalamusMiceModels, AnimalNeuronsConceptsVesicular 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 ResearchMeSH Keywords5-MethylcytosineAgouti-Related ProteinAnimalsAnti-Anxiety AgentsChromatinDioxygenasesGamma-Aminobutyric AcidHumansHypothalamusLeptinMiceNeuronsNeuropeptide YConceptsAgRP 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 ResearchMeSH KeywordsAgouti-Related ProteinAnimalsDopaminergic NeuronsHypothalamusMiceNeuropeptide YPrefrontal CortexConceptsMedial 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 ResearchMeSH KeywordsAgouti-Related ProteinAnimalsDiabetes Mellitus, Type 2Feeding BehaviorHumansHyperphagiaLysophospholipidsMiceNeuronsSynapsesConceptsFasting-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 levels
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 ResearchMeSH KeywordsAgouti-Related ProteinAnimalsAstrocytesHungerHypothalamusMaleMiceMice, TransgenicNeuronal PlasticityNeuronsReceptors, Prostaglandin E, EP2 SubtypeConceptsAgRP 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 ResearchMeSH KeywordsAgouti-Related ProteinAnimalsBody WeightDynaminsEnergy MetabolismFastingFeeding BehaviorFemaleMaleMiceNeuronsConceptsAgRP 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 utilization
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
2017
Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus
Morozov YM, Koch M, Rakic P, Horvath TL. Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus. Molecular Metabolism 2017, 6: 374-381. PMID: 28377876, PMCID: PMC5369208, DOI: 10.1016/j.molmet.2017.01.004.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusAxonsMiceMice, Inbred C57BLNeuropeptide YReceptor, Cannabinoid, CB1
2015
AgRP 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 integrityHypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding
Dietrich MO, Zimmer MR, Bober J, Horvath TL. Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding. Cell 2015, 160: 1222-1232. PMID: 25748653, PMCID: PMC4484787, DOI: 10.1016/j.cell.2015.02.024.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsAnxietyBehavior, AnimalCapsaicinFeeding BehaviorFemaleGABA AntagonistsHypothalamusMaleNeuronsStereotyped BehaviorTRPV Cation ChannelsConceptsHypothalamic AgRP neuronsAgRP neuronsNeuropeptidergic signalingReceptor signalingFunctional rolePotential therapeutic avenuesAgRP neuron activationStereotypic behaviorFeeding behaviorRepetitive behaviorsSignalingTherapeutic avenuesFood triggersAdult miceNervous systemDecreased anxietyNeuronsMinor effectActivationFood consumptionNeuron activationGoal-directed behaviorSensory informationFlexible goal-directed behaviorDisease
2014
O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat
Ruan HB, Dietrich MO, Liu ZW, Zimmer MR, Li MD, Singh JP, Zhang K, Yin R, Wu J, Horvath TL, Yang X. O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat. Cell 2014, 159: 306-317. PMID: 25303527, PMCID: PMC4509746, DOI: 10.1016/j.cell.2014.09.010.Peer-Reviewed Original ResearchConceptsAgRP neuronsFundamental cellular processesWhite fatN-acetylglucosamine (O-GlcNAc) modificationOrexigenic AgRP neuronsVoltage-dependent potassium channelsCellular processesGlcNAc transferaseDynamic physiological processesNuclear proteinsWhite adipose tissue browningPhysiological processesAdipose tissue browningDiet-induced obesityPhysiological relevanceTissue browningGenetic ablationBeige cellsEnergy metabolismInsulin resistanceNeuronal excitabilityPotassium channelsAdipose tissueCentral mechanismsNeuronsMolecular and cellular regulation of hypothalamic melanocortin neurons controlling food intake and energy metabolism
Koch M, Horvath TL. Molecular and cellular regulation of hypothalamic melanocortin neurons controlling food intake and energy metabolism. Molecular Psychiatry 2014, 19: 752-761. PMID: 24732669, DOI: 10.1038/mp.2014.30.Peer-Reviewed Original ResearchConceptsHypothalamic melanocortin neuronsEnergy metabolismFood intakePotential functional interactionsMelanocortin neuronsCellular regulationCellular processesFunctional interactionNeuronal circuit activityCellular mechanismsPhysiological behaviorEnergy homeostasisMetabolic eventsRegulationHypothalamic neuronsMetabolic healthObese individualsChronic overloadGlial cellsPhysical activityMetabolic disordersMelanocortin systemNeuronal circuitryCentral connectionsPsychiatric diseases
2013
Mitochondrial Dynamics Controlled by Mitofusins Regulate Agrp Neuronal Activity and Diet-Induced Obesity
Dietrich MO, Liu ZW, Horvath TL. Mitochondrial Dynamics Controlled by Mitofusins Regulate Agrp Neuronal Activity and Diet-Induced Obesity. Cell 2013, 155: 188-199. PMID: 24074868, PMCID: PMC4142434, DOI: 10.1016/j.cell.2013.09.004.Peer-Reviewed Original ResearchConceptsMitochondrial dynamicsEnergy metabolismCell-type specificCellular energy metabolismWhole-body energy metabolismKey organellesMitofusin 1Mitofusin 2High-fat dietMitochondria sizeAgRP neuronsMfn1Anorexigenic pro-opiomelanocortin (POMC) neuronsAgRP neuronal activityKnockout miceMetabolismPro-opiomelanocortin (POMC) neuronsFusion mechanismDiet-Induced ObesityMitofusinsOverfed stateImportant roleCellsDynamic changesOrganelles
2012
Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis
Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Reports 2012, 13: 1079-1086. PMID: 23146889, PMCID: PMC3512417, DOI: 10.1038/embor.2012.174.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAgouti-Related ProteinBrainEnergy MetabolismGlucoseHomeostasisHumansInsulinInsulin SecretionLeptinObesityProprotein ConvertasesSignal TransductionConceptsGlucose homeostasisEnergy homeostasisPrevalence of obesityWhole-body energy homeostasisBody energy homeostasisAnorectic hormonesAgRP neuronsObese patientsProtein (AgRP) neuronsCentral effectsHypothalamic proopiomelanocortinBody weightInsulin actionLeptinHormonal actionMajor targetInsulin pathwayHomeostasisInsulinNeuronsHormoneBrainLatest findingsEnergy balanceSteady riseAgRP neurons: a switch between peripheral carbohydrate and lipid utilization
Varela L, Horvath TL. AgRP neurons: a switch between peripheral carbohydrate and lipid utilization. The EMBO Journal 2012, 31: 4252-4254. PMID: 23085989, PMCID: PMC3501218, DOI: 10.1038/emboj.2012.287.Peer-Reviewed Original ResearchAgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors
Dietrich MO, Bober J, Ferreira JG, Tellez LA, Mineur YS, Souza DO, Gao XB, Picciotto MR, Araújo I, Liu ZW, Horvath TL. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors. Nature Neuroscience 2012, 15: 1108-1110. PMID: 22729177, PMCID: PMC3411867, DOI: 10.1038/nn.3147.Peer-Reviewed Original ResearchFoxO1 Target Gpr17 Activates AgRP Neurons to Regulate Food Intake
Ren H, Orozco IJ, Su Y, Suyama S, Gutiérrez-Juárez R, Horvath TL, Wardlaw SL, Plum L, Arancio O, Accili D. FoxO1 Target Gpr17 Activates AgRP Neurons to Regulate Food Intake. Cell 2012, 149: 1314-1326. PMID: 22682251, PMCID: PMC3613436, DOI: 10.1016/j.cell.2012.04.032.Peer-Reviewed Original ResearchConceptsFood intakeAgRP neuronsG-protein-coupled receptor GPR17Intracerebroventricular injectionHypothalamic neuronsReceptor GPR17Pharmacological modulationGlucose homeostasisNutritional statusTherapeutic potentialMice resultsGenetic ablationNeuronsFoxO1 ablationIntakeSatietyGPR17InsulinExpression profilingAblationPathwayCangrelorObesityLeptinAgonistsAgRP neurons: The foes of reproduction in leptin-deficient obese subjects
Dietrich MO, Horvath TL. AgRP neurons: The foes of reproduction in leptin-deficient obese subjects. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 2699-2700. PMID: 22323603, PMCID: PMC3286927, DOI: 10.1073/pnas.1121355109.Peer-Reviewed Original Research
2011
Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism
Diano S, Horvath TL. Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism. Trends In Molecular Medicine 2011, 18: 52-58. PMID: 21917523, DOI: 10.1016/j.molmed.2011.08.003.Peer-Reviewed Original ResearchConceptsProtein 2Lipid metabolismExcess of nutrientsHypothalamic neuronal circuitsNutrient availabilityPeripheral tissue functionsPhysiological functionsMetabolism regulationChronic diseasesMetabolism-related chronic diseasesTissue functionFuture therapeutic strategiesPathological processesPeripheral mechanismsLipid levelsNeuronal circuitsTherapeutic strategiesMetabolismImpairs healthMitochondriaDiseaseUCP2GlucoseRegulationNutrients