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 cellsTET3Obesity
2021
Astrocytic lipid metabolism determines susceptibility to diet-induced obesity
Varela L, Kim JG, Fernández-Tussy P, Aryal B, Liu ZW, Fernández-Hernando C, Horvath TL. Astrocytic lipid metabolism determines susceptibility to diet-induced obesity. Science Advances 2021, 7: eabj2814. PMID: 34890239, DOI: 10.1126/sciadv.abj2814.Peer-Reviewed Original ResearchDiet-induced obesityHypothalamic astrocytesPeroxisome proliferator-activated receptor gammaHypothalamic neuronal circuitsProliferator-activated receptor gammaControl of feedingFatty acid homeostasisSystemic glucoseMetabolic milieuGlucose homeostasisBody weightReceptor gammaSynaptic plasticityNeuronal circuitsNutrient sensingLipid metabolismCellular adaptationObesityAstrocytesAcid homeostasisUnidentified roleFA metabolismEnergy metabolismElevated susceptibilityAvailability of FA
2019
Mitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging
Seli E, Wang T, Horvath TL. Mitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging. Fertility And Sterility 2019, 111: 197-204. PMID: 30691623, DOI: 10.1016/j.fertnstert.2018.11.048.Peer-Reviewed Original ResearchConceptsMitochondrial unfolded protein responseTwo-cell embryo developmentUnfolded protein responseImpaired oocyte maturationMorphology of mitochondriaMitochondrial dysfunction resultsPremature reproductive agingNovel mechanistic insightsMitochondrial DNA contentReactive oxygen species productionPrevention of agingCLPP resultsProtein responseOxygen species productionReproductive agingPreimplantation embryosAge-related accumulationOxidative phosphorylationStress responseEmbryo developmentForm blastocystsMitochondrial functionMitochondriaMitochondrial dysfunctionEnergy metabolism
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 signals
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 settingsMetabolismGliaEstrogenNeurons4.19 Obesity and Appetite: Central Control Mechanisms
Horvath T. 4.19 Obesity and Appetite: Central Control Mechanisms. 2017, 369-376. DOI: 10.1016/b978-0-12-803592-4.00085-7.Peer-Reviewed Original ResearchLate-onset chronic diseasesChronic diseasesPrevalence of obesitySerious comorbiditiesFat massTissue malignancyParkinson's diseaseCardiovascular disordersCentral control mechanismAlzheimer's diseaseDiseaseEpigenetic vulnerabilityCellular energy metabolismObesityVulnerable individualsEnergy metabolismAppetiteDisordersTissueDifferent tissuesComorbiditiesDiabetesMajor roleMalignancySatiety
2015
Estrogen- and Satiety State-Dependent Metabolic Lateralization in the Hypothalamus of Female Rats
Toth I, Kiss DS, Jocsak G, Somogyi V, Toronyi E, Bartha T, Frenyo LV, Horvath TL, Zsarnovszky A. Estrogen- and Satiety State-Dependent Metabolic Lateralization in the Hypothalamus of Female Rats. PLOS ONE 2015, 10: e0137462. PMID: 26339901, PMCID: PMC4560379, DOI: 10.1371/journal.pone.0137462.Peer-Reviewed Original ResearchConceptsAd libitum fed animalsFemale ratsRight-sided dominanceSatiety stateFed animalsOvariectomized female ratsContribution of estrogenMetabolic differencesHours of fastingIntensity of cellsState 3 mitochondrial respirationHypothalamic functionMetabolic asymmetryTissue metabolismHypothalamusEstrogenProportion of animalsHypothalamic asymmetryRatsAd libitumLateralizationHigher centersMitochondrial respiration rateEnergy metabolismGhrelin
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
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 diseasesMinireview: 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
Ghrelin Regulation of Learning, Memory, and Neurodegeneration
Horvath T. Ghrelin Regulation of Learning, Memory, and Neurodegeneration. Contemporary Endocrinology 2012, 171-180. DOI: 10.1007/978-1-61779-903-7_9.Peer-Reviewed Original ResearchLate-onset chronic diseasesChronic diseasesGut-derived hormonesCause of morbidityChronic disease developmentGhrelin regulationGhrelin actionPeripheral mechanismsBrain healthTissue malignancyCardiovascular disordersParkinson's diseaseCalorie restrictionBrain functionDiseaseProlongs longevityEpigenetic vulnerabilityFinancial burdenGhrelinCellular energy metabolismDisease developmentEnergy metabolismIntegrative physiologyTissueHealthPlasticity 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
2010
An Oscillatory Switch in mTOR Kinase Activity Sets Regulatory T Cell Responsiveness
Procaccini C, De Rosa V, Galgani M, Abanni L, Calì G, Porcellini A, Carbone F, Fontana S, Horvath TL, La Cava A, Matarese G. An Oscillatory Switch in mTOR Kinase Activity Sets Regulatory T Cell Responsiveness. Immunity 2010, 33: 929-941. PMID: 21145759, PMCID: PMC3133602, DOI: 10.1016/j.immuni.2010.11.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4 AntigensCell ProliferationCells, CulturedClonal AnergyDisease ProgressionEncephalomyelitis, Autoimmune, ExperimentalForkhead Transcription FactorsHumansInterleukin-2Interleukin-2 Receptor alpha SubunitLeptinMiceMice, Inbred C57BLSignal TransductionSirolimusT-Lymphocytes, RegulatoryTOR Serine-Threonine KinasesConceptsTreg cellsAnergic stateInterleukin-2Treg cell expansionRegulatory T cellsExogenous interleukin-2T cell responsivenessCell receptor stimulationImmune toleranceT cellsCell responsivenessReceptor stimulationMTOR activationEarly downregulationMammalian targetMTOR kinase activityRapamycin (mTOR) pathwayProliferative capabilityTransient inhibitionUnderlying mechanismElevated activityEnergy metabolismCellsResponsivenessCell expansionGonadotropin-Releasing Hormone Fibers Contact POMC Neurons in the Hypothalamic Arcuate Nucleus
Sotonyi P, Mezei G, Racz B, Dallman MF, Abizaid A, Horvath TL. Gonadotropin-Releasing Hormone Fibers Contact POMC Neurons in the Hypothalamic Arcuate Nucleus. Reproductive Sciences 2010, 17: 1024-1028. PMID: 20713970, DOI: 10.1177/1933719110378346.Peer-Reviewed Original ResearchConceptsArcuate nucleusGonadotropin-releasing hormone (GnRH) neuronsPOMC cell bodiesEnergy expenditureHypothalamic arcuate nucleusHypothalamic neuronal populationsMelanocyte stimulating hormoneHormone neuronsPOMC neuronsAnorexigenic proopiomelanocortinStimulating hormoneAnatomical proximityAxon terminalsGonadal axisGlucose homeostasisPeripheral signalsNeuronal populationsCell bodiesDirect appositionGnRHEnergy metabolismNeuronsMetabolic stateHormoneProopiomelanocortin
2009
Feeding signals and brain circuitry
Dietrich MO, Horvath TL. Feeding signals and brain circuitry. European Journal Of Neuroscience 2009, 30: 1688-1696. PMID: 19878280, DOI: 10.1111/j.1460-9568.2009.06963.x.Peer-Reviewed Original ResearchA 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 basis