2018
Insulin regulates POMC neuronal plasticity to control glucose metabolism
Dodd GT, Michael NJ, Lee-Young RS, Mangiafico SP, Pryor JT, Munder AC, Simonds SE, Brüning JC, Zhang ZY, Cowley MA, Andrikopoulos S, Horvath TL, Spanswick D, Tiganis T. Insulin regulates POMC neuronal plasticity to control glucose metabolism. ELife 2018, 7: e38704. PMID: 30230471, PMCID: PMC6170188, DOI: 10.7554/elife.38704.Peer-Reviewed Original ResearchConceptsHepatic glucose productionPOMC neuronsSuch adaptive processesNutritional cuesGene expressionMolecular mechanismsGlucose metabolismInsulin receptorDiet-induced obesityTCPTPNeuronal plasticityAdaptive processHypothalamic neuronsNeuronal excitabilityGlucose productionMetabolismInsulinNeuronsRepressionNeural responsesObesityRegulationMechanismPlasticityExpression
2014
Mitochondrial dynamics in the central regulation of metabolism
Nasrallah CM, Horvath TL. Mitochondrial dynamics in the central regulation of metabolism. Nature Reviews Endocrinology 2014, 10: 650-658. PMID: 25200564, DOI: 10.1038/nrendo.2014.160.Peer-Reviewed Original ResearchConceptsPOMC neuronsMetabolic disordersPeripheral tissue functionsCentral melanocortin systemMitochondrial dynamicsProopiomelanocortin neuronsAnorexigenic responseOrexigenic responseHypothalamic neuronsCentral regulationMelanocortin systemNeuronsDistinct signaling pathwaysSignaling pathwaysMitochondrial fusionMolecular regulatorsTissue functionDistinct functionsDisordersFatty acidsMetabolismActivationObesityAppetiteResponseMolecular 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
Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses
Matarese G, Procaccini C, Menale C, Kim JG, Kim JD, Diano S, Diano N, De Rosa V, Dietrich MO, Horvath TL. Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 6193-6198. PMID: 23530205, PMCID: PMC3625304, DOI: 10.1073/pnas.1210644110.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAllelesAnimalsAntigensAutoimmunityCatalytic DomainEncephalomyelitis, Autoimmune, ExperimentalFlow CytometryFood DeprivationForkhead Transcription FactorsGenetic Predisposition to DiseaseHumansHungerHypothalamusInflammationMiceMice, KnockoutMice, TransgenicMyelin SheathNeuronsSirtuin 1Thymus GlandT-Lymphocytes, RegulatoryConceptsRegulatory T cell responsesDelayed-type hypersensitivity responseHypothalamic feeding circuitsPeptide-expressing neuronsRegulatory T cellsSympathetic nervous systemT cell responsesForkhead box P3T helper 1Adaptive immune responsesWhole-body energy metabolismLow energy availabilityT cell activationAutoimmune disease susceptibilityBox P3Hypothalamic agoutiThymic generationHelper 1Hypersensitivity responseProinflammatory cytokinesHypothalamic neuronsSuppressive capacityT cellsImmune responseNervous system
2012
Phosphoribosomes for Fingerprinting Neurons
Dietrich MO, Horvath TL. Phosphoribosomes for Fingerprinting Neurons. Cell 2012, 151: 934-936. PMID: 23178116, DOI: 10.1016/j.cell.2012.11.006.Peer-Reviewed Original ResearchGhrelin-immunopositive hypothalamic neurons tie the circadian clock and visual system to the lateral hypothalamic arousal center
Horvath TL, Abizaid A, Dietrich MO, Li Y, Takahashi JS, Bass J. Ghrelin-immunopositive hypothalamic neurons tie the circadian clock and visual system to the lateral hypothalamic arousal center. Molecular Metabolism 2012, 1: 79-85. PMID: 24024121, PMCID: PMC3757645, DOI: 10.1016/j.molmet.2012.08.003.Peer-Reviewed Original ResearchHypothalamic neuronsOrexin/hypocretin neuronsOrexin/hypocretin systemUnique anatomical distributionDirect synaptic inputGrowth hormone releaseLateral geniculate nucleusHypothalamic arousal systemsHypocretin neuronsHypothalamic slicesGeniculate nucleusHormone releaseHypocretin systemAnatomical distributionArousal centersSynaptic inputsVisual centersGhrelin mRNAGhrelinArousal systemNeuronsKey mediatorCircadian patternSuprachiasmatic nucleusElectrophysiological activityFoxO1 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 profilingAblationPathwayCangrelorObesityLeptinAgonists
2011
Differential Acute and Chronic Effects of Leptin on Hypothalamic Astrocyte Morphology and Synaptic Protein Levels
García-Cáceres C, Fuente-Martín E, Burgos-Ramos E, Granado M, Frago LM, Barrios V, Horvath T, Argente J, Chowen JA. Differential Acute and Chronic Effects of Leptin on Hypothalamic Astrocyte Morphology and Synaptic Protein Levels. Endocrinology 2011, 152: 1809-1818. PMID: 21343257, PMCID: PMC3860256, DOI: 10.1210/en.2010-1252.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic proteinChronic leptin exposureSynaptic inputsAstrocyte morphologyLeptin exposureGFAP levelsGlial structural proteinsSynaptic protein densityChronic leptin administrationAcute leptin treatmentSynaptic protein levelsAdult male ratsCentral leptin resistanceFibrillary acidic proteinLevels 1 hPossible direct effectGlial ensheathingNeonatal overnutritionGlial activationLeptin levelsLeptin administrationHypothalamic neuronsLeptin resistanceLeptin treatmentMale rats
2010
Estrogen Promotes Parvalbumin Expression in Arcuate Nucleus POMC Neurons
Sotonyi P, Gao Q, Bechmann I, Horvath TL. Estrogen Promotes Parvalbumin Expression in Arcuate Nucleus POMC Neurons. Reproductive Sciences 2010, 17: 1077-1080. PMID: 20713969, DOI: 10.1177/1933719110379651.Peer-Reviewed Original ResearchConceptsPOMC neuronsArcuate nucleus neuronsLean body massSuppression of feedingSuppress appetiteParvalbumin expressionEstrogen treatmentHypothalamic neuronsArcuate nucleusNeuronal degenerationNucleus neuronsFemale miceCalcium overloadExcitatory activityCalcium-binding proteinsCalcium influxReceptor presenceCalcium entrySustained satietyNeuronsEnergy expenditureEstradiolParvalbuminAppetiteBody massEarly-Life Experience Reduces Excitation to Stress-Responsive Hypothalamic Neurons and Reprograms the Expression of Corticotropin-Releasing Hormone
Korosi A, Shanabrough M, McClelland S, Liu ZW, Borok E, Gao XB, Horvath TL, Baram TZ. Early-Life Experience Reduces Excitation to Stress-Responsive Hypothalamic Neurons and Reprograms the Expression of Corticotropin-Releasing Hormone. Journal Of Neuroscience 2010, 30: 703-713. PMID: 20071535, PMCID: PMC2822406, DOI: 10.1523/jneurosci.4214-09.2010.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnalysis of VarianceAnimalsAnimals, NewbornChromatin ImmunoprecipitationCorticotropin-Releasing HormoneExcitatory Amino Acid AntagonistsFemaleGene Expression Regulation, DevelopmentalMaleMaternal DeprivationMicroscopy, Electron, TransmissionNeuronsParaventricular Hypothalamic NucleusPatch-Clamp TechniquesPhysical StimulationPregnancyRatsRats, Sprague-DawleyRepressor ProteinsRNA, MessengerSodium Channel BlockersStress, PsychologicalSynaptic PotentialsTetrodotoxinVesicular Glutamate Transport Protein 2ConceptsCorticotropin-releasing hormoneNeuron-restrictive silencer factorCRH neuronsHypothalamic neuronsCRH expressionEarly life experiencesMiniature excitatory synaptic currentsHypothalamic CRH neuronsExcitatory synaptic currentsCRH gene expressionGlutamate vesicular transporterCRH gene transcriptionTranscriptional repressor neuron-restrictive silencer factorExcitatory innervationExperience-induced neuroplasticityInhibitory synapsesRat pupsExcitatory synapsesSynaptic currentsPersistent suppressionVesicular transportersCognitive functionNeuronsSilencer factorMaternal care
2009
A Serotonin-Dependent Mechanism Explains the Leptin Regulation of Bone Mass, Appetite, and Energy Expenditure
Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL, Karsenty G. A Serotonin-Dependent Mechanism Explains the Leptin Regulation of Bone Mass, Appetite, and Energy Expenditure. Cell 2009, 138: 976-989. PMID: 19737523, PMCID: PMC2768582, DOI: 10.1016/j.cell.2009.06.051.Peer-Reviewed Original ResearchConceptsSerotonergic neuronsHypothalamic neuronsBone massEnergy expenditureVentromedial hypothalamic neuronsBone mass accrualSerotonin-dependent mechanismRegulation of appetiteEnergy expenditure phenotypesSpecific hypothalamic neuronsHtr2c receptorLeptin deficiencyArcuate neuronsLeptin inhibitionSerotonin synthesisLeptin receptorLeptin regulationLeptinNeuronsAppetiteReceptorsEnergy metabolismBrainBoneMolecular basisLeptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding
Leinninger GM, Jo YH, Leshan RL, Louis GW, Yang H, Barrera JG, Wilson H, Opland DM, Faouzi MA, Gong Y, Jones JC, Rhodes CJ, Chua S, Diano S, Horvath TL, Seeley RJ, Becker JB, Münzberg H, Myers MG. Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding. Cell Metabolism 2009, 10: 89-98. PMID: 19656487, PMCID: PMC2723060, DOI: 10.1016/j.cmet.2009.06.011.Peer-Reviewed Original ResearchConceptsLateral hypothalamic areaVentral tegmental areaMesolimbic DA systemLepRb neuronsMesolimbic dopamine systemLeptin actionLeptin receptorDopamine systemDA systemLeptin-deficient animalsLateral hypothalamic neuronsAnorexigenic hormone leptinLeptin actsHypothalamic areaHypothalamic neuronsSuppress feedingHormone leptinTegmental areaDA contentInhibitory neuronsRate-limiting enzymeBody weightNeuronsLeptinReceptors
2008
Fuel utilization by hypothalamic neurons: roles for ROS
Horvath TL, Andrews ZB, Diano S. Fuel utilization by hypothalamic neurons: roles for ROS. Trends In Endocrinology And Metabolism 2008, 20: 78-87. PMID: 19084428, DOI: 10.1016/j.tem.2008.10.003.Peer-Reviewed Original ResearchConceptsEnergy homeostasisFree radical productionAnorexigenic neuronsNeuronal doctrineArcuate nucleusHypothalamic neuronsHypothalamic outputMelanocortin systemEffect of glucoseNeuronal functionFree radical formationSpecific neuronsAcid levelsNeuronsAmino acid levelsNeurobiological aspectsRadical productionEvidence pointsFatty acidsFuel sensingIntracellular substratesHomeostasisNutritional signalsGlucoseHypothalamus
2007
Estrogen-Induced Hypothalamic Synaptic Plasticity and Pituitary Sensitization in the Control of the Estrogen-Induced Gonadotrophin Surge
Naftolin F, Garcia-Segura LM, Horvath TL, Zsarnovszky A, Demir N, Fadiel A, Leranth C, Vondracek-Klepper S, Lewis C, Chang A, Parducz A. Estrogen-Induced Hypothalamic Synaptic Plasticity and Pituitary Sensitization in the Control of the Estrogen-Induced Gonadotrophin Surge. Reproductive Sciences 2007, 14: 101-116. PMID: 17636222, DOI: 10.1177/1933719107301059.Peer-Reviewed Original ResearchConceptsGnRH secretionPituitary gonadotrophsGonadotrophin surgeSynaptic plasticityInsulinlike growth factor 1Triggering of ovulationOvarian estrogen secretionGrowth factor-1Neural cell adhesion moleculePituitary sensitizationGnRH cellsGnRH neuronsEstrogen secretionHypothalamic neuronsGonadal functionCell adhesion moleculeSex steroidsSpecific immunoneutralizationOvarian cycleGonadotrophsAdhesion moleculesEstrogenMaximal sensitizationSecretionFactor 1
2006
gp130 signaling in proopiomelanocortin neurons mediates the acute anorectic response to centrally applied ciliary neurotrophic factor
Janoschek R, Plum L, Koch L, Münzberg H, Diano S, Shanabrough M, Müller W, Horvath TL, Brüning JC. gp130 signaling in proopiomelanocortin neurons mediates the acute anorectic response to centrally applied ciliary neurotrophic factor. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 10707-10712. PMID: 16818888, PMCID: PMC1502296, DOI: 10.1073/pnas.0600425103.Peer-Reviewed Original ResearchConceptsCiliary neurotrophic factorAnorectic effectPOMC neuronsNeurotrophic factorCNTF actionAcute anorectic responseNormal energy homeostasisHigh-fat dietStress-induced anorexiaC-fos expressionProopiomelanocortin neuronsAnorectic responseHypothalamic neuronsLeptin resistanceFat dietParaventricular nucleusUnaltered numberKnockout micePOMC cellsCommon cytokinesEnergy homeostasisNeuronsSTAT3 phosphorylationExact siteCre-loxP
2004
Direct visual and circadian pathways target neuroendocrine cells in primates
Abizaid A, Horvath B, Keefe DL, Leranth C, Horvath TL. Direct visual and circadian pathways target neuroendocrine cells in primates. European Journal Of Neuroscience 2004, 20: 2767-2776. PMID: 15548220, DOI: 10.1111/j.1460-9568.2004.03737.x.Peer-Reviewed Original ResearchConceptsSuprachiasmatic nucleusRetinal inputNeuroendocrine cellsDirect retinal inputHormone-releasing hormoneNon-human primatesHypothalamic suprachiasmatic nucleusSCN efferentsHypothalamic areaHypothalamic neuronsHypothalamic sitesMonosynaptic pathwayVisual afferentsHypothalamic regulatorGonadal axisHormone releaseNeuroendocrine functionPituitary gonadotropsPhotic modulationNeuronsCircadian pacemakerVervet monkeysPresent studyTracing techniquesCircadian clockCentral Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats
Tang-Christensen M, Vrang N, Ortmann S, Bidlingmaier M, Horvath TL, Tschöp M. Central Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats. Endocrinology 2004, 145: 4645-4652. PMID: 15231700, DOI: 10.1210/en.2004-0529.Peer-Reviewed Original ResearchConceptsNeuropeptides neuropeptide YFood intakePhysical activityLocomotor activityOrexigenic neuropeptides neuropeptide YCentral administrationSpontaneous physical activitySingle intracerebroventricular injectionMajor etiological factorGH secretagogue receptorSpontaneous locomotor activityOverall locomotor activityDose-dependent mannerNovel peptide hormoneGhrelin injectionIntracerebroventricular injectionHypothalamic neuronsNeuropeptide YSecretagogue receptorEtiological factorsGhrelinHigh doseEndogenous ligandHunger factorAgRP
1993
Aromatase immunoreactivity in the rat brain: Gonadectomy-sensitive hypothalamic neurons and an unresponsive “limbic ring” of the lateral septum-bed nucleus-amygdala complex
Jakab RL, Horvath TL, Leranth C, Harada N, Naftolin F. Aromatase immunoreactivity in the rat brain: Gonadectomy-sensitive hypothalamic neurons and an unresponsive “limbic ring” of the lateral septum-bed nucleus-amygdala complex. The Journal Of Steroid Biochemistry And Molecular Biology 1993, 44: 481-498. PMID: 8476763, DOI: 10.1016/0960-0760(93)90253-s.Peer-Reviewed Original ResearchConceptsAromatase-immunoreactive neuronsRat brainAromatase systemStria terminalisLateral septal areaDorsomedial hypothalamic nucleusCentral amygdaloid nucleusMidline thalamic regionAxon-like processesDorsolateral hypothalamic areaNeuron systemConversion of androgensLaterodorsal divisionSubincertal nucleusHuman placental aromataseAromatase immunoreactivityBrain distributionGonadectomized ratsHypothalamic areaHypothalamic neuronsAmygdaloid nucleusLimbic areasHypothalamic nucleiZona incertaSeptal area