2024
Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation
Mohr S, Dai Pra R, Platt M, Feketa V, Shanabrough M, Varela L, Kristant A, Cao H, Merriman D, Horvath T, Bagriantsev S, Gracheva E. Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation. Nature Communications 2024, 15: 5803. PMID: 38987241, PMCID: PMC11236985, DOI: 10.1038/s41467-024-49996-2.Peer-Reviewed Original ResearchConceptsHypothalamic feeding centersHormone deficiencyHypothalamic arcuate nucleus neuronsArcuate nucleus neuronsThyroid hormone deficiencyFeeding centerEffects of ghrelinAnorexigenic effectNucleus neuronsPhysiological anorexiaThyroid hormonesNormal physiological functionsGround squirrelsInterbout arousalAnorexiaThirteen-lined ground squirrelsProlonged periodReduced sensitivityPhysiological functionsDeficiency
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
2016
Hypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis
Jin S, Kim JG, Park JW, Koch M, Horvath TL, Lee BJ. Hypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis. Scientific Reports 2016, 6: 29424. PMID: 27405276, PMCID: PMC4942617, DOI: 10.1038/srep29424.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnorexiaArcuate Nucleus of HypothalamusCyclooxygenase InhibitorsEnergy MetabolismFeverInflammationLipopeptidesMaleMiceMice, KnockoutMicrogliaMyeloid Differentiation Factor 88NF-kappa BPro-OpiomelanocortinRatsReceptor, Melanocortin, Type 3Receptor, Melanocortin, Type 4Toll-Like Receptor 2Weight LossConceptsSickness behaviorHypothalamic inflammationToll-like receptor 2 (TLR2) activationSickness behavior symptomsNuclear factor kappa BBody weight lossReceptor 2 activationFactor kappa BNeuronal circuit functionHypothalamic microgliaProopiomelanocortin neuronsInflammatory mechanismsIntracerebroventricular injectionPathophysiologic mechanismsTLR2 activationInflammatory processCyclooxygenase pathwayNeuronal activationKappa BBehavior symptomsWeight lossInput organizationMicrogliaTLR2Inflammation
2009
Nesfatin-1-Regulated Oxytocinergic Signaling in the Paraventricular Nucleus Causes Anorexia through a Leptin-Independent Melanocortin Pathway
Maejima Y, Sedbazar U, Suyama S, Kohno D, Onaka T, Takano E, Yoshida N, Koike M, Uchiyama Y, Fujiwara K, Yashiro T, Horvath TL, Dietrich MO, Tanaka S, Dezaki K, Oh-I S, Hashimoto K, Shimizu H, Nakata M, Mori M, Yada T. Nesfatin-1-Regulated Oxytocinergic Signaling in the Paraventricular Nucleus Causes Anorexia through a Leptin-Independent Melanocortin Pathway. Cell Metabolism 2009, 10: 355-365. PMID: 19883614, DOI: 10.1016/j.cmet.2009.09.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnorexiaAutocrine CommunicationCalcium-Binding ProteinsDNA-Binding ProteinsLeptinMelanocortinsMiceNerve Tissue ProteinsNeuroendocrine CellsNucleobindinsOxytocinParacrine CommunicationParaventricular Hypothalamic NucleusPro-OpiomelanocortinRatsRats, ZuckerSignal TransductionSolitary NucleusConceptsNucleus tractus solitariusNesfatin-1Oxytocin releaseParacrine/autocrine actionsNesfatin-1 neuronsParaventricular nucleus functionPro-opiomelanocortin (POMC) neuronsZucker fatty ratsOxytocin receptor antagonistOxytocin terminalsPVN neuronsTractus solitariusReceptor antagonistCentral injectionParaventricular nucleusAutocrine actionMelanocortin pathwayNeuronal activityNeural pathwaysPVNAnorexiaNeuronsNucleus functionOxytocinImmunoelectron micrographs
2006
Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals
Gao Q, Mezei G, Nie Y, Rao Y, Choi CS, Bechmann I, Leranth C, Toran-Allerand D, Priest CA, Roberts JL, Gao XB, Mobbs C, Shulman GI, Diano S, Horvath TL. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nature Medicine 2006, 13: 89-94. PMID: 17195839, DOI: 10.1038/nm1525.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnorexiaArcuate Nucleus of HypothalamusBody WeightEstradiolEstrogen Receptor alphaExcitatory Postsynaptic PotentialsFemaleInjections, IntraventricularLeptinMaleMelanocortinsMiceMice, Inbred C57BLMice, KnockoutMice, ObeseMicroscopy, ElectronNeuronsObesityOvariectomyPro-OpiomelanocortinRatsRats, Sprague-DawleySignal TransductionSTAT3 Transcription FactorConceptsArcuate nucleusFood intakeLeptin receptor-deficient miceGonadal steroid estradiolRearrangement of synapsesReceptor-deficient miceBody weight regulationBody weight gainWild-type ratsPOMC neuronsLeptin effectsExcitatory inputsMetabolic hormonesLeptin receptorObese animalsSteroids estradiolWeight regulationBody weightSynaptic plasticityWeight gainRobust increaseInput organizationSTAT3 activationEnergy expenditureAdipositygp130 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
2005
Agouti-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
2001
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley M, Smart J, Rubinstein M, Cerdán M, Diano S, Horvath T, Cone R, Low M. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001, 411: 480-484. PMID: 11373681, DOI: 10.1038/35078085.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnimals, Genetically ModifiedAnorexiaArcuate Nucleus of HypothalamusElectrophysiologyEvoked PotentialsGamma-Aminobutyric AcidGreen Fluorescent ProteinsLeptinLuminescent ProteinsMaleMiceMice, Inbred C57BLNerve NetNeural InhibitionNeuronsNeuropeptide YPro-OpiomelanocortinConceptsAnorexigenic POMC neuronsPOMC neuronsArcuate nucleusLeptin actionLeptin-deficient humansLepob/Lepob miceLeptin receptor expressionLong-term energy balanceNonspecific cation channelGABA neuronsOrexigenic neuropeptidesObese humansAdipocyte hormoneNeuropeptide YLeptin resistanceElevated leptinReceptor expressionLepob miceMelanocortin peptidesTransgenic miceLeptinAction potentialsNeuropeptide modulatorsCommon obesityElectrophysiological recordings