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 cellsTET3ObesityVentromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity
Wang Q, Zhang B, Stutz B, Liu ZW, Horvath TL, Yang X. Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity. Science Advances 2022, 8: eabn8092. PMID: 36044565, PMCID: PMC9432828, DOI: 10.1126/sciadv.abn8092.Peer-Reviewed Original ResearchConceptsVentromedial hypothalamusWhite adipose tissueVMH neuronsAdipose tissueBody weightLipid metabolismRapid weight gainCounterregulatory responsesSympathetic activitySympathetic innervationAdipocyte hypertrophyTissue lipolysisNeuronal excitabilityFood intakePhysical activityObesity phenotypesGenetic ablationWeight gainHomeostatic set pointEnergy expenditureNeuronsInnervationLipolysisSignificant changesCellular sensors
2021
Drp1 is required for AgRP neuronal activity and feeding
Jin S, Yoon NA, Liu ZW, Song JE, Horvath TL, Kim JD, Diano S. Drp1 is required for AgRP neuronal activity and feeding. ELife 2021, 10: e64351. PMID: 33689681, PMCID: PMC7946429, DOI: 10.7554/elife.64351.Peer-Reviewed Original ResearchConceptsAgRP neuronal activityFatty acid oxidationAgRP neuronsNeuronal activityAgRP neuronal functionHypothalamic AgRP neuronsBody weight regulationMitochondrial fatty acid utilizationWhole-body energy homeostasisHypothalamic orexigenic agoutiFatty acid utilizationAcid oxidationFat massCKO miceNeuronal activationPeptide-1Body weightNeuronal functionOrexigenic agoutiEnergy homeostasisMitochondrial fissionSignificant decreaseEnergy expenditureNeuronsAcid utilization
2020
Functional Aspects of Hypothalamic Asymmetry
Kiss DS, Toth I, Jocsak G, Barany Z, Bartha T, Frenyo LV, Horvath TL, Zsarnovszky A. Functional Aspects of Hypothalamic Asymmetry. Brain Sciences 2020, 10: 389. PMID: 32575391, PMCID: PMC7349050, DOI: 10.3390/brainsci10060389.Peer-Reviewed Original ResearchFunctional lateralizationFunctional asymmetryHigher brain functionsHypothalamic controlSmall brain regionsCirculatory functionBrain areasReproductive functionBrain regionsBrain functionBrain halvesHypothalamic asymmetryEnergy expenditureBrain processingBody temperatureHypothalamusHomeostatic processesCircadian rhythmHemispheric specializationLateralizationData highlightPrevious studies
2016
Feeding Behavior: Hypocretin/Orexin Neurons Act between Food Seeking and Eating
Gao XB, Horvath TL. Feeding Behavior: Hypocretin/Orexin Neurons Act between Food Seeking and Eating. Current Biology 2016, 26: r845-r847. PMID: 27676302, DOI: 10.1016/j.cub.2016.07.069.Peer-Reviewed Original Research
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
2014
PPARγ ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding
Long L, Toda C, Jeong JK, Horvath TL, Diano S. PPARγ ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding. Journal Of Clinical Investigation 2014, 124: 4017-4027. PMID: 25083994, PMCID: PMC4151211, DOI: 10.1172/jci76220.Peer-Reviewed Original ResearchConceptsHigh-fat dietPOMC neuronsFood intakeImproved glucose metabolismHigh-fat feedingWhole-body energy balanceBody weight gainProopiomelanocortin neuronsPeripheral administrationFat massLeptin sensitivityControl animalsGlucose metabolismBody weightPPARγ activatorsLocomotor activityEnergy homeostasisPPARγWeight gainNeuronsSelective ablationEnergy expenditureIntakeNuclear receptorsMice
2013
Mitofusin 2 in POMC Neurons Connects ER Stress with Leptin Resistance and Energy Imbalance
Schneeberger M, Dietrich MO, Sebastián D, Imbernón M, Castaño C, Garcia A, Esteban Y, Gonzalez-Franquesa A, Rodríguez IC, Bortolozzi A, Garcia-Roves PM, Gomis R, Nogueiras R, Horvath TL, Zorzano A, Claret M. Mitofusin 2 in POMC Neurons Connects ER Stress with Leptin Resistance and Energy Imbalance. Cell 2013, 155: 172-187. PMID: 24074867, PMCID: PMC3839088, DOI: 10.1016/j.cell.2013.09.003.Peer-Reviewed Original ResearchConceptsHypothalamic ER stressER stress-induced leptin resistanceLeptin resistanceMitofusin 2ER stressMitochondria-endoplasmic reticulum interactionAnorexigenic pro-opiomelanocortin (POMC) neuronsPro-opiomelanocortin (POMC) neuronsDiet-induced obesityMitochondria-ER contactsSystemic energy balancePOMC neuronsMetabolic alterationsCausative factorsEnergy expenditurePOMC processingObesityUnderlying mechanismCrucial involvementNeuronsEnergy imbalanceEssential regulatorCritical roleHyperphagiaHypothalamus
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 mammalsFeedingObesityDiabetesHippocampusCortexHormoneBrainNeuroendocrine Regulation of Energy Metabolism
Dietrich M, Horvath T. Neuroendocrine Regulation of Energy Metabolism. Endocrinology And Metabolism 2012, 27: 268-273. DOI: 10.3803/enm.2012.27.4.268.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPeripheral metabolic signalsEnergy expenditureBrain homeostatic systemsMechanism of actionBrain involvementChronic regulationPharmacological techniquesNeuronal controlNeuroendocrine regulationNeuronal mechanismsEnergy homeostasisComplex feeding behaviorHomeostatic systemMetabolic signalsReview articleFeeding behaviorInvolvementCurrent understandingBrain
2011
Ghrelin-induced hypothermia: A physiological basis but no clinical risk
Wiedmer P, Strasser F, Horvath TL, Blum D, DiMarchi R, Lutz T, Schürmann A, Joost HG, Tschöp MH, Tong J. Ghrelin-induced hypothermia: A physiological basis but no clinical risk. Physiology & Behavior 2011, 105: 43-51. PMID: 21513721, PMCID: PMC3146973, DOI: 10.1016/j.physbeh.2011.03.027.Peer-Reviewed Original ResearchConceptsGhrelin treatmentBody temperatureApplication of ghrelinMedial preoptic areaPotential anatomical basisCold-sensitive neuronsGhrelin infusionBody core temperatureChronic i.Positive energy balanceGhrelin receptorPreoptic areaAxon terminalsClinical riskFood intakeGhrelinHealthy humansSerious hypothermiaMale subjectsPhysiologic circumstancesAnatomical basisHypothermiaCold exposureRelevant decreaseEnergy expenditureEffects of chronic weight perturbation on energy homeostasis and brain structure in mice
Ravussin Y, Gutman R, Diano S, Shanabrough M, Borok E, Sarman B, Lehmann A, LeDuc CA, Rosenbaum M, Horvath TL, Leibel RL. Effects of chronic weight perturbation on energy homeostasis and brain structure in mice. AJP Regulatory Integrative And Comparative Physiology 2011, 300: r1352-r1362. PMID: 21411766, PMCID: PMC3119157, DOI: 10.1152/ajpregu.00429.2010.Peer-Reviewed Original ResearchConceptsDiet-induced obeseEnergy expenditureArcuate nucleus proopiomelanocortin neuronsWeight lossWeight-reduced individualsSustained weight lossReduced body weightObese human subjectsCentral nervous systemHuman subjectsSustained weight gainProopiomelanocortin neuronsBody massUpward resettingMale miceExcitatory synapsesBody fatMouse modelBody weightNervous systemSynaptic changesPersistent decreaseEnergy homeostasisWeight gainBrain structures
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 massGonadotropin-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
Divergent Regulation of Energy Expenditure and Hepatic Glucose Production by Insulin Receptor in Agouti-Related Protein and POMC Neurons
Lin HV, Plum L, Ono H, Gutiérrez-Juárez R, Shanabrough M, Borok E, Horvath TL, Rossetti L, Accili D. Divergent Regulation of Energy Expenditure and Hepatic Glucose Production by Insulin Receptor in Agouti-Related Protein and POMC Neurons. Diabetes 2009, 59: 337-346. PMID: 19933998, PMCID: PMC2809966, DOI: 10.2337/db09-1303.Peer-Reviewed Original ResearchConceptsHepatic glucose productionAgRP neuronsPOMC neuronsInsulin receptorEnergy expenditureInsulin actionGlucose productionInhibitory synaptic contactsSulfonylurea receptor 1 (SUR1) subunitsCentral nervous systemL1 miceProopiomelanocortin neuronsHypothalamic insulinDivergent regulationInsulin resistanceSynaptic contactsInsulin suppressionGlucose metabolismHypothalamic deficiencyNervous systemLocomotor activityDecreased expressionEnergy homeostasisINSRNeuronsA 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
2008
Ghrelin: an orexigenic signal from the stomach
Horvath T. Ghrelin: an orexigenic signal from the stomach. 2008, 266-284. DOI: 10.1017/cbo9780511541643.010.Peer-Reviewed Original ResearchEffects of ghrelinGrowth hormone secretagoguesFood intakeGrowth hormoneGrowth hormone secretagogue receptorDiscovery of ghrelinAmino acid peptide hormoneAnorectic hormonesOrexigenic signalsGhrelin actionPeripheral mechanismsSecretagogue receptorMetabolic effectsHormone secretagoguesBody fatGhrelinPeripheral signalsEndogenous ligandStimulatory effectEnergy expenditurePeptide hormonesCell proliferationIntakeHormoneHormonal regulationCross-talk between estrogen and leptin signaling in the hypothalamus
Gao Q, Horvath TL. Cross-talk between estrogen and leptin signaling in the hypothalamus. AJP Endocrinology And Metabolism 2008, 294: e817-e826. PMID: 18334610, DOI: 10.1152/ajpendo.00733.2007.Peer-Reviewed Original ResearchConceptsAdipocyte-secreted hormone leptinGonadal steroid hormone estrogenAction of leptinMajor risk factorNeuroendocrine reproductive axisEnergy expenditureHalf of adultsSteroid hormone estrogenEnhanced food intakeFunction of estrogenEstrogen deficiencyRisk factorsHormone leptinCardiovascular diseaseHormone estrogenFood intakeBody fatReproductive axisLeptinEstrogenRegulation of reproductionEnergy homeostasisWeight gainEstrogen facilitatesNeuroendocrine processes
2007
Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation
Plum L, Rother E, Münzberg H, Wunderlich FT, Morgan DA, Hampel B, Shanabrough M, Janoschek R, Könner AC, Alber J, Suzuki A, Krone W, Horvath TL, Rahmouni K, Brüning JC. Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation. Cell Metabolism 2007, 6: 431-445. PMID: 18054313, DOI: 10.1016/j.cmet.2007.10.012.Peer-Reviewed Original ResearchConceptsWhite adipose tissueSympathetic nerve activityBrown adipose tissuePI3k activationAdipose tissueLeptin-deficient ob/obOb/ob miceUnaltered body weightEnergy expenditureOb/obLeptin-sensitive neuronsNerve activityEndogenous leptinOb miceBody weightUCP1 expressionWAT morphologyEnergy homeostasisLeptinSkeletal muscleMicePTEN ablationSignaling pathwaysMitochondrial contentDirect genetic evidenceSimultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure
Pfluger PT, Kirchner H, Günnel S, Schrott B, Perez-Tilve D, Fu S, Benoit SC, Horvath T, Joost HG, Wortley KE, Sleeman MW, Tschöp M. Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure. AJP Gastrointestinal And Liver Physiology 2007, 294: g610-g618. PMID: 18048479, DOI: 10.1152/ajpgi.00321.2007.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAnthropometryBlood GlucoseBody CompositionBody TemperatureBody WeightEatingEnergy MetabolismGene DeletionGenotypeGhrelinGlucose Tolerance TestInsulin ResistanceLigandsLipidsMiceMice, KnockoutMotor ActivityReceptors, GhrelinReverse Transcriptase Polymerase Chain ReactionRNA, MessengerConceptsFood intakeSimultaneous deletionStandard dietHigh-fat diet-induced obesityMotor activityWild-type control miceFirst mouse mutantsMetabolic phenotypeDiet-induced obesityEnergy metabolism phenotypesEnergy expenditureGene-deficient miceKnockout mice exhibitSingle gene-deficient miceSame genetic backgroundMost speciesWT miceControl miceStandard chowMolecular controlBody adiposityBiological roleLean massMouse mutantsMeal patterns