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 cellsTET3ObesityParaventricular glia drive circuit function to control metabolism
Varela L, Horvath TL. Paraventricular glia drive circuit function to control metabolism. Cell Metabolism 2022, 34: 1424-1426. PMID: 36198288, DOI: 10.1016/j.cmet.2022.09.012.Peer-Reviewed Original Research
2018
Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
García-Cáceres C, Balland E, Prevot V, Luquet S, Woods SC, Koch M, Horvath TL, Yi CX, Chowen JA, Verkhratsky A, Araque A, Bechmann I, Tschöp MH. Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism. Nature Neuroscience 2018, 22: 7-14. PMID: 30531847, DOI: 10.1038/s41593-018-0286-y.Peer-Reviewed Original ResearchConceptsControl of metabolismNon-neuronal cellsNeuronal-glial networksFunctional interactionSpecific neuronal subpopulationsEnergy metabolismHypothalamic feeding circuitsRole of astrocytesPhysiological responsesGlial-neuronal interactionsMetabolismFood-related cuesNeuronal subpopulationsSystemic metabolismFood intakeBrain controlMetabolic statusRecent advancesMicrogliaAstrocytesGeneticsTanycytesComplex setBiologyInteroceptive signalsInsulin 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
2017
Cannabis in fat: high hopes to treat obesity
Hawkins MN, Horvath TL. Cannabis in fat: high hopes to treat obesity. Journal Of Clinical Investigation 2017, 127: 3918-3920. PMID: 29035279, PMCID: PMC5663345, DOI: 10.1172/jci97042.Peer-Reviewed Original ResearchConceptsCannabinoid receptor type 1Body weightNovel peripheral targetsReduced body weightSystemic metabolic changesAdipocyte-specific deletionReceptor type 1Sympathetic toneTotal adiposityCNS effectsPeripheral mechanismsSystemic metabolismPeripheral targetsAdipocyte physiologyAdipose tissueType 1Metabolic changesMetabolic profileEnergy metabolismMetabolismAdiposityObesityCausal relationshipMiceMacrophagesThyroid hormone- and estrogen receptor interactions with natural ligands and endocrine disruptors in the cerebellum
Zsarnovszky A, Kiss D, Jocsak G, Nemeth G, Toth I, Horvath TL. Thyroid hormone- and estrogen receptor interactions with natural ligands and endocrine disruptors in the cerebellum. Frontiers In Neuroendocrinology 2017, 48: 23-36. PMID: 28987779, DOI: 10.1016/j.yfrne.2017.10.001.Peer-Reviewed Original ResearchConceptsEffects of phytoestrogensThyroid hormonesBrain functionNormal physiological settingsMetabolic parametersMature brainEstrogen receptor interactionSteroid hormonesBrain developmentHormoneHomeostatic parametersIntercellular actionsHormonal mechanismsReceptor interactionNatural ligandEnergy metabolismCerebellumEndocrine disruptorsPhytoestrogensPivotal rolePhysiological settingsMetabolismGliaEstrogenNeurons
2016
Metabolism and Mental Illness
Sestan-Pesa M, Horvath TL. Metabolism and Mental Illness. Trends In Molecular Medicine 2016, 22: 174-183. PMID: 26776095, DOI: 10.1016/j.molmed.2015.12.003.Peer-Reviewed Original ResearchConceptsCentral nervous systemMental illnessBasic metabolic principlesHigher brain functionsCerebral cortexNovel therapiesNervous systemBrain functionSystemic controlPathological conditionsIllnessAppetiteCrucial regulatorFuture research strategiesOverwhelming evidenceMetabolic principlesFeeding behaviorMetabolismHypothalamusTherapyCortexBrain
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 integrityGhrelin
Müller T, Nogueiras R, Andermann M, Andrews Z, Anker S, Argente J, Batterham R, Benoit S, Bowers C, Broglio F, Casanueva F, D'Alessio D, Depoortere I, Geliebter A, Ghigo E, Cole P, Cowley M, Cummings D, Dagher A, Diano S, Dickson S, Diéguez C, Granata R, Grill H, Grove K, Habegger K, Heppner K, Heiman M, Holsen L, Holst B, Inui A, Jansson J, Kirchner H, Korbonits M, Laferrère B, LeRoux C, Lopez M, Morin S, Nakazato M, Nass R, Perez-Tilve D, Pfluger P, Schwartz T, Seeley R, Sleeman M, Sun Y, Sussel L, Tong J, Thorner M, van der Lely A, van der Ploeg L, Zigman J, Kojima M, Kangawa K, Smith R, Horvath T, Tschöp M. Ghrelin. Molecular Metabolism 2015, 4: 437-460. PMID: 26042199, PMCID: PMC4443295, DOI: 10.1016/j.molmet.2015.03.005.Peer-Reviewed Original ResearchGastrointestinal peptide hormone ghrelinGrowth hormone secretagogue receptorSleep/wake rhythmGastric acid secretionSystemic energy metabolismPeptide hormone ghrelinPeripheral actionsGut motilitySecretagogue receptorHormone ghrelinAcid secretionGlucose metabolismGhrelinEndogenous ligandTaste sensationEnergy metabolismSecretionMetabolismDiverse biological functionsYearsHormone
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 acidsMetabolismActivationObesityAppetiteResponseMinireview: Metabolism of Female Reproduction: Regulatory Mechanisms and Clinical Implications
Seli E, Babayev E, Collins SC, Nemeth G, Horvath TL. Minireview: Metabolism of Female Reproduction: Regulatory Mechanisms and Clinical Implications. Endocrinology 2014, 28: 790-804. PMID: 24678733, PMCID: PMC4042071, DOI: 10.1210/me.2013-1413.Peer-Reviewed Original ResearchConceptsFemale reproductionPeripheral availabilityMetabolic disturbancesMetabolic hormonesAnorexia nervosaClinical implicationsMetabolic determinantsHuman reproductionEnergy metabolismFemale fertilityMetabolic stateMetabolismCentral processesMellitusObesityHypothalamusRegulatory mechanismsInfertilityHormoneNervosa
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 changesOrganellesHypothalamic control of energy balance: insights into the role of synaptic plasticity
Dietrich MO, Horvath TL. Hypothalamic control of energy balance: insights into the role of synaptic plasticity. Trends In Neurosciences 2013, 36: 65-73. PMID: 23318157, DOI: 10.1016/j.tins.2012.12.005.Peer-Reviewed Original ResearchConceptsWhole-body energy metabolismRegion-specific expressionGenetic toolsPeripheral tissue functionsMetabolism regulationMetabolic hormone receptorsEnergy metabolismTissue functionMetabolic eventsRole of neuronsHormone receptorsRegulationGlial cellsHypothalamic controlSynaptic plasticityCentral regulationNeuronal circuitsBrain circuitsEnormous leapPlasticitySurprising findingRoleExpressionMetabolismDynamic process
2012
Plasticity of Brain Feeding Circuits in Response to Food
Horvath T. Plasticity of Brain Feeding Circuits in Response to Food. 2012, 61-74. DOI: 10.1007/978-1-4614-3492-4_5.Peer-Reviewed Original ResearchBrain regionsBrain structuresBrain's feeding circuitsPrevalent medical problemEnergy expenditureHigher brain regionsSleep/wake cycleEnergy metabolismPeripheral hormonesAutonomic functionCerebral cortexNeuronal circuitsMedical problemsNeuronal interactionsWake cycleFeeding circuitMetabolismMost mammalsFeedingObesityDiabetesHippocampusCortexHormoneBrain
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
2010
Regulatory T cells in obesity: the leptin connection
Matarese G, Procaccini C, De Rosa V, Horvath TL, La Cava A. Regulatory T cells in obesity: the leptin connection. Trends In Molecular Medicine 2010, 16: 247-256. PMID: 20493774, DOI: 10.1016/j.molmed.2010.04.002.Peer-Reviewed Original ResearchConceptsTreg cellsResident Treg cellsRegulatory T cellsAdipocyte-derived hormonePathogenesis of obesityT cell responsivenessChronic inflammationHypothalamic levelT cellsFood intakeCell responsivenessGlucose homeostasisAdipose tissueTherapeutic interventionsNutritional statusObesityRecent findingsCellsTissueMetabolismInflammationLeptinPathogenesisHormoneIntake