2015
Reducing Adiposity in a Critical Developmental Window Has Lasting Benefits in Mice
Lerea JS, Ring LE, Hassouna R, Chong AC, Szigeti-Buck K, Horvath TL, Zeltser LM. Reducing Adiposity in a Critical Developmental Window Has Lasting Benefits in Mice. Endocrinology 2015, 157: 666-678. PMID: 26587784, PMCID: PMC4733128, DOI: 10.1210/en.2015-1753.Peer-Reviewed Original ResearchConceptsDietary interventionBrown adipose tissue thermogenesisWeight lossEarly-onset hyperphagiaRapid weight regainEarly-onset obesityEnergy expenditureAdipose tissue thermogenesisCritical developmental windowWeight regainSympathetic toneMetabolic improvementHypothalamic leptinTissue thermogenesisEarly interventionCompensatory decreaseUnfavorable responseMiceMost adultsObesityAdiposityInterventionDevelopmental windowAdultsBrown adipose tissue mitochondria
2013
Intranasal epidermal growth factor treatment rescues neonatal brain injury
Scafidi J, Hammond TR, Scafidi S, Ritter J, Jablonska B, Roncal M, Szigeti-Buck K, Coman D, Huang Y, McCarter RJ, Hyder F, Horvath TL, Gallo V. Intranasal epidermal growth factor treatment rescues neonatal brain injury. Nature 2013, 506: 230-234. PMID: 24390343, PMCID: PMC4106485, DOI: 10.1038/nature12880.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAnimalsAnimals, NewbornBrain InjuriesCell DifferentiationCell DivisionCell LineageCell SurvivalDemyelinating DiseasesDisease Models, AnimalEpidermal Growth FactorErbB ReceptorsHumansHypoxiaInfant, Premature, DiseasesMaleMiceMolecular Targeted TherapyOligodendrogliaRegenerationSignal TransductionStem CellsTime FactorsConceptsDiffuse white matter injuryNeonatal brain injuryVery preterm infantsWhite matter injuryOligodendrocyte precursor cellsEpidermal growth factor receptorGrowth factor treatmentGrowth factor receptorPreterm infantsFunctional recoveryBrain injurySuch injuriesEpidermal growth factor treatmentMouse modelFactor treatmentInjuryFactor receptorPrecursor cellsInfantsReceptors
2011
Obesity is associated with hypothalamic injury in rodents and humans
Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW. Obesity is associated with hypothalamic injury in rodents and humans. Journal Of Clinical Investigation 2011, 122: 153-162. PMID: 22201683, PMCID: PMC3248304, DOI: 10.1172/jci59660.Peer-Reviewed Original ResearchConceptsHigh-fat dietHFD feedingMediobasal hypothalamusPeripheral tissuesRodent modelsBody weight controlHypothalamic arcuate nucleusSubstantial weight gainConsequences of obesityNeuron injuryHypothalamic injuryNeuronal injuryNeuroprotective mechanismsReactive gliosisObese humansHypothalamic areaArcuate nucleusInflammatory signalingBrain areasWeight controlObesityGliosisEnergy homeostasisWeight gainInflammationHigh-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons
Klöckener T, Hess S, Belgardt BF, Paeger L, Verhagen LA, Husch A, Sohn JW, Hampel B, Dhillon H, Zigman JM, Lowell BB, Williams KW, Elmquist JK, Horvath TL, Kloppenburg P, Brüning JC. High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons. Nature Neuroscience 2011, 14: 911-918. PMID: 21642975, PMCID: PMC3371271, DOI: 10.1038/nn.2847.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAge FactorsAnimalsAnimals, NewbornBlood GlucoseBody WeightCalorimetryDietary FatsDose-Response Relationship, DrugEatingEnzyme InhibitorsEnzyme-Linked Immunosorbent AssayFemaleGene Expression RegulationGlucose Tolerance TestGreen Fluorescent ProteinsHypoglycemic AgentsIn Vitro TechniquesInjections, IntraventricularInsulinLeptinMaleMiceMice, Inbred C57BLMice, TransgenicNeuronsObesityPatch-Clamp TechniquesPhosphatidylinositol 3-KinasesReceptor, InsulinRNA, MessengerSignal TransductionSteroidogenic Factor 1Time FactorsTolbutamideVentromedial Hypothalamic NucleusDifferential 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
Enhanced anorexigenic signaling in lean obesity resistant syndecan-3 null mice
Zheng Q, Zhu J, Shanabrough M, Borok E, Benoit SC, Horvath TL, Clegg DJ, Reizes O. Enhanced anorexigenic signaling in lean obesity resistant syndecan-3 null mice. Neuroscience 2010, 171: 1032-1040. PMID: 20923696, PMCID: PMC2991621, DOI: 10.1016/j.neuroscience.2010.09.060.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAlpha-MSHAnalysis of VarianceAnimalsBody WeightDose-Response Relationship, DrugEatingFeeding BehaviorFood DeprivationGene Expression RegulationMaleMiceMice, KnockoutNeuronsNeuropeptide YParaventricular Hypothalamic NucleusProto-Oncogene Proteins c-fosSignal TransductionSyndecan-3Time FactorsConceptsMelanocortin agonist melanotan IISyndecan-3 null miceParaventricular nucleusBody weightNull miceHypothalamic target neuronsNeuropeptide α-MSHRisk of diabetesC-Fos immunoreactivityHypothalamic paraventricular nucleusBody weight regulationWild-type miceTypes of cancerAnorexigenic αAgRP neuronsHormone neuronsHypothalamic circuitsNeuropeptide YAnorexigenic signalingNeuropeptide responsesCardiovascular diseaseFood intakeTarget neuronsMelanotan IIType mice
2009
Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice
Blum ID, Patterson Z, Khazall R, Lamont EW, Sleeman MW, Horvath TL, Abizaid A. Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice. Neuroscience 2009, 164: 351-359. PMID: 19666088, PMCID: PMC2996828, DOI: 10.1016/j.neuroscience.2009.08.009.Peer-Reviewed Original ResearchConceptsAnticipatory locomotor activityGHSR KO miceLocomotor activityKO miceGhrelin receptor deficient miceReceptor-deficient miceFeeding scheduleFos expression patternsWild-type littermatesRestricted feeding scheduleGhrelin receptor geneGhrelin injectionOrexigenic hormoneFos immunoreactivityHypothalamic nucleiDeficient miceLocomotor responseGhrelinH dailyMiceReceptor geneMealH patternTargeted mutationsBehavioral measures
2006
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschöp MH, Gao XB, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal Of Clinical Investigation 2006, 116: 3229-3239. PMID: 17060947, PMCID: PMC1618869, DOI: 10.1172/jci29867.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAppetiteDopamineFluorescent Antibody TechniqueGhrelinMaleMesencephalonMiceMice, Inbred C57BLMice, KnockoutNeuronsNucleus AccumbensPatch-Clamp TechniquesPeptide HormonesRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, GhrelinTime FactorsVentral Tegmental AreaConceptsVentral tegmental areaGHSR-deficient miceGHSR-dependent mannerGut hormone ghrelinDopamine neuronal activityMidbrain dopamine neuronsMesolimbic reward circuitrySynaptic input organizationPeripheral ghrelinRebound feedingVTA administrationOrexigenic effectDopamine turnoverGHSR antagonistDopamine neuronsHypothalamic centersTegmental areaHormone ghrelinNucleus accumbensGhrelinNeuronal activitySynapse formationReward circuitryInput organizationFeeding schedule
2005
A Novel Growth Hormone Secretagogue-1a Receptor Antagonist That Blocks Ghrelin-Induced Growth Hormone Secretion but Induces Increased Body Weight Gain
Halem HA, Taylor JE, Dong JZ, Shen Y, Datta R, Abizaid A, Diano S, Horvath TL, Culler MD. A Novel Growth Hormone Secretagogue-1a Receptor Antagonist That Blocks Ghrelin-Induced Growth Hormone Secretion but Induces Increased Body Weight Gain. Neuroendocrinology 2005, 81: 339-349. PMID: 16210868, DOI: 10.1159/000088796.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArea Under CurveBehavior, AnimalBinding, CompetitiveBody WeightBrainCell CountCHO CellsCricetinaeCricetulusDose-Response Relationship, DrugDrug InteractionsFeeding BehaviorGhrelinGrowth HormoneHumansImmunohistochemistryIodine IsotopesMaleOncogene Proteins v-fosPeptide HormonesRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, GhrelinTime FactorsConceptsDorsal medial hypothalamusGHS-1a receptorGrowth hormone secretionBIM-28163Fos-IRWeight gainGH secretionHormone secretionGrowth hormone secretagogue 1a receptorAntagonist of ghrelinMedial arcuate nucleusAction of ghrelinFos protein immunoreactivityAnti-obesity strategiesBody weight gainGhrelin activationConcomitant administrationGhrelin actionMedial hypothalamusArcuate nucleusReceptor antagonistGhrelin receptorFood intakeProtein immunoreactivityHuman ghrelinAgouti-related peptide–expressing neurons are mandatory for feeding
Gropp E, Shanabrough M, Borok E, Xu AW, Janoschek R, Buch T, Plum L, Balthasar N, Hampel B, Waisman A, Barsh GS, Horvath TL, Brüning JC. Agouti-related peptide–expressing neurons are mandatory for feeding. Nature Neuroscience 2005, 8: 1289-1291. PMID: 16158063, DOI: 10.1038/nn1548.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsAnorexiaArcuate Nucleus of HypothalamusBeta-GalactosidaseBody WeightCell CountDiphtheria ToxinEatingFeeding BehaviorGene Expression RegulationIntercellular Signaling Peptides and ProteinsMiceMice, KnockoutNeuronsNeuropeptide YPro-OpiomelanocortinProteinsTime Factors
2004
Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation
Gao Q, Wolfgang MJ, Neschen S, Morino K, Horvath TL, Shulman GI, Fu XY. Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 4661-4666. PMID: 15070774, PMCID: PMC384803, DOI: 10.1073/pnas.0303992101.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAdipose Tissue, BrownAnimalsBody Temperature RegulationCorticosteroneDiabetes MellitusDNA-Binding ProteinsFemaleInfertility, FemaleInfertility, MaleIntermediate Filament ProteinsKineticsLeptinMaleMiceMice, KnockoutMice, TransgenicNerve Tissue ProteinsNestinObesityRatsSTAT3 Transcription FactorTime FactorsTrans-ActivatorsConceptsSignal transducerActivator of transcriptionApparent developmental abnormalitiesEnergy homeostasisGenetic modelsTranscription 3Mendelian ratioHomozygous mutantsCold stressNeonatal lethalityPhysiological roleMutantsGlial differentiationUnique phenotypeSTAT3Essential roleDevelopmental abnormalitiesHomeostasisActivatorNeuroendocrine defectsTranscriptionDisruptionProteinKnockoutReproduction
2002
Leptin Uptake by Serotonergic Neurones of the Dorsal Raphe
Fernández‐Galaz M, Diano S, Horvath TL, Garcia‐Segura L. Leptin Uptake by Serotonergic Neurones of the Dorsal Raphe. Journal Of Neuroendocrinology 2002, 14: 429-434. PMID: 12047717, DOI: 10.1046/j.1365-2826.2002.00783.x.Peer-Reviewed Original ResearchConceptsEffects of leptinRaphe nucleusDorsal rapheFemale ratsMidbrain serotonergic systemsSerotonergic systemSerotonergic neuronesRaphe neuronesDistribution of neuronesMouse recombinant leptinIntracerebroventricular administrationLeptin administrationLeptin uptakeLeptin treatmentPeriventricular grayMale ratsFood intakeRecombinant leptinLeptinSleep patternsGender differencesBrain functionImportant mediatorLeptin accumulationNeurones
2001
A GABA-neuropeptide Y (NPY) interplay in LH release
Horvath T, Pu S, Dube M, Diano S, Kalra S. A GABA-neuropeptide Y (NPY) interplay in LH release. Peptides 2001, 22: 473-481. PMID: 11287104, DOI: 10.1016/s0196-9781(01)00343-6.Peer-Reviewed Original ResearchConceptsGamma-amino butyric acidLH releaseNeurotransmitter/neuromodulatorExcitatory effectsArcuate nucleusReceptor agonistInhibitory gamma-amino butyric acidY4 receptor agonistRelease of LHImmunoreactive axon terminalsRat brain sectionsDose-dependent mannerOvarian steroidsOvariectomized ratsAxon terminalsBrain sectionsPrimary siteNPYMorphological findingsCyclic releaseAgonistsLHNeuromodulatorsRatsAdministration