2024
GLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective
D’Ávila M, Hall S, Horvath T. GLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective. Endocrinology 2024, 165: bqae128. PMID: 39301751, DOI: 10.1210/endocr/bqae128.Peer-Reviewed Original ResearchHypothalamic 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 functionsDeficiencyKisspeptin signaling in astrocytes modulates the reproductive axis
Torres E, Pellegrino G, Granados-Rodríguez M, Fuentes-Fayos A, Velasco I, Coutteau-Robles A, Legrand A, Shanabrough M, Perdices-Lopez C, Leon S, Yeo S, Manchishi S, Sánchez-Tapia M, Navarro V, Pineda R, Roa J, Naftolin F, Argente J, Luque R, Chowen J, Horvath T, Prevot V, Sharif A, Colledge W, Tena-Sempere M, Romero-Ruiz A. Kisspeptin signaling in astrocytes modulates the reproductive axis. Journal Of Clinical Investigation 2024, 134: e172908. PMID: 38861336, PMCID: PMC11291270, DOI: 10.1172/jci172908.Peer-Reviewed Original ResearchResponse to metabolic stressProtein-protein interactionsMetabolic stressOntology analysisReproductive axisKisspeptin signalingGene expressionKisspeptin actionHypothalamic GnRH neuronsProteomic profilingFemale pubertal onsetReproductive modulesExpression of KISS1RLH secretory profilesSignaling-pathwayCellular co-expressionConditional ablationResponse to kisspeptinLH responses to kisspeptinNon-neuronal pathwaysAstrocytes in vivoHigh-fat dietGFAP-positive cellsPathwayReproductive controlCancer-associated hypercalcemia signals through the hindbrain to cause anorexia
Grinman D, Dann P, Shanabrough M, Horvath T, Wysolmerski J. Cancer-associated hypercalcemia signals through the hindbrain to cause anorexia. Journal Of Bone Oncology 2024, 45: 100535. DOI: 10.1016/j.jbo.2024.100535.Peer-Reviewed Original ResearchmicroRNA-33 controls hunger signaling in hypothalamic AgRP neurons
Price N, Fernández-Tussy P, Varela L, Cardelo M, Shanabrough M, Aryal B, de Cabo R, Suárez Y, Horvath T, Fernández-Hernando C. microRNA-33 controls hunger signaling in hypothalamic AgRP neurons. Nature Communications 2024, 15: 2131. PMID: 38459068, PMCID: PMC10923783, DOI: 10.1038/s41467-024-46427-0.Peer-Reviewed Original ResearchConceptsAgRP neuronsFeeding behaviorFatty acid metabolismNon-coding RNAsMitochondrial biogenesisRegulatory pathwaysTarget genesHypothalamic AgRP neuronsExcessive nutrient intakeCentral regulatorBioenergetic processesAcid metabolismActivation of AgRP neuronsModulate feeding behaviorCentral regulation of feeding behaviorRegulation of feeding behaviorMiR-33Hunger signalsMicroRNA-33Metabolic diseasesAlternative therapeutic approachLoss of miR-33Mouse modelMetabolic dysfunctionRegulation
2023
A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model
Lv H, Catarino J, Li D, Liu B, Gao X, Horvath T, Huang Y. A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300015120. PMID: 37036983, PMCID: PMC10120042, DOI: 10.1073/pnas.2300015120.Peer-Reviewed Original ResearchConceptsVesicular GABA transporterActivity-based anorexiaExpression of AgRPNeuropeptide YAgRP neuronsAnorexia nervosaAnxiety/depressive-like behaviorsHypothalamic AgRP neuronsDepressive-like behaviorCurrent treatment optionsHigh relapse rateStress-related disordersHuman neuronal cellsNutritional supportRelapse rateTreatment optionsAnxiolytic effectsPsychiatric illnessMouse modelAnimal modelsHigh mortalityGABA transporterGenetic ablationNeuronal cellsNeuronsNeonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice
Stevens H, Scuderi S, Collica S, Tomasi S, Horvath T, Vaccarino F. Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice. Translational Psychiatry 2023, 13: 89. PMID: 36906620, PMCID: PMC10008554, DOI: 10.1038/s41398-023-02372-y.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptor 2Anxiety-like behaviorAttention deficit hyperactivity disorderAstroglial cellsGrowth factor receptor 2Reduced anxiety-like behaviorGlia-neuron interactionsAstroglial cell functionEarly postnatal periodFactor receptor 2Early postnatal lossPostnatal mouse brainWeeks of ageDeficit hyperactivity disorderGlial cellsGlutamine synthetase expressionBehavioral deficitsPostnatal periodReceptor 2Floxed miceHGFAP-CreMouse brainNeonatal lossPostnatal astrogliaPostnatal lossResponse to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect
Takahashi T, Stoiljkovic M, Song E, Gao X, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu Z, Kristant A, Zhang Y, Sulkowski P, Glazer P, Kaczmarek L, Horvath T, Iwasaki A. Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect. Neuron 2023, 111: 612-613. PMID: 36863323, DOI: 10.1016/j.neuron.2023.02.006.Peer-Reviewed Original ResearchImpaired Ghrelin Signaling Does Not Lead to Alterations of Anxiety-like Behaviors in Adult Mice Chronically Exposed to THC during Adolescence
Sestan-Pesa M, Shanabrough M, Horvath T, Miletta M. Impaired Ghrelin Signaling Does Not Lead to Alterations of Anxiety-like Behaviors in Adult Mice Chronically Exposed to THC during Adolescence. Biomedicines 2023, 11: 144. PMID: 36672651, PMCID: PMC9855766, DOI: 10.3390/biomedicines11010144.Peer-Reviewed Original ResearchAnxiety-like behaviorGrowth hormone secretagogue receptorTHC exposureAdult miceGHSR knockout miceDepression-like behaviorLate adolescenceWild-type littermatesLong-term useGHSR signalingGhrelin signalingSecretagogue receptorKnockout miceAnimal modelsTetrahydrocannabinol (THC) administrationMental illnessMiceSignificant alterationsGhrelinMarijuana useAdolescenceReceptorsProlonged periodExposureLong-term impact
2022
Ghrelin Predicts Stimulant and Sedative Effects of Alcohol in Heavy Drinkers
Ralevski E, Horvath T, Shanabrough M, Newcomb J, Pisani E, Petrakis I. Ghrelin Predicts Stimulant and Sedative Effects of Alcohol in Heavy Drinkers. Alcohol And Alcoholism 2022, 58: 100-106. PMID: 36382470, PMCID: PMC9830489, DOI: 10.1093/alcalc/agac058.Peer-Reviewed Original ResearchA hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice
Korchynska S, Rebernik P, Pende M, Boi L, Alpár A, Tasan R, Becker K, Balueva K, Saghafi S, Wulff P, Horvath TL, Fisone G, Dodt HU, Hökfelt T, Harkany T, Romanov RA. A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice. Nature Communications 2022, 13: 5944. PMID: 36209152, PMCID: PMC9547883, DOI: 10.1038/s41467-022-33584-3.Peer-Reviewed Original ResearchConceptsLateral septumDopamine neuronsSuprachiasmatic nucleusSomatostatin-containing neuronsStimulation ex vivoAmphetamine-induced hyperlocomotionRegulation of locomotionDopamine outputChemogenetic inhibitionNeuropeptidergic innervationPeriventricular nucleusChemogenetic manipulationHypothalamic lociSynaptic targetsAnterior subdivisionEx vivoBrain clockNeuronsSedentary periodL activityHyperlocomotionCellular targetsMicePeVNInnervationTET3 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 ResearchLINE-1 activation in the cerebellum drives ataxia
Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu ZW, Kristant A, Zhang Y, Sulkowski P, Glazer PM, Kaczmarek LK, Horvath TL, Iwasaki A. LINE-1 activation in the cerebellum drives ataxia. Neuron 2022, 110: 3278-3287.e8. PMID: 36070749, PMCID: PMC9588660, DOI: 10.1016/j.neuron.2022.08.011.Peer-Reviewed Original ResearchConceptsLINE-1 activationL1 activationAtaxia telangiectasia patientsNuclear element-1Transposable elementsEpigenetic silencersHuman genomeL1 promoterMolecular regulatorsDNA damagePurkinje cell dysfunctionElement 1First direct evidenceTelangiectasia patientsDirect targetingCerebellar expressionNeurodegenerative diseasesDisease etiologyCalcium homeostasisVentromedial 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 sensorsTREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-β-Related Hippocampal Pathophysiology in Mice
Stoiljkovic M, Gutierrez KO, Kelley C, Horvath TL, Hajós M. TREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-β-Related Hippocampal Pathophysiology in Mice. Journal Of Alzheimer's Disease 2022, 88: 837-847. PMID: 34120899, PMCID: PMC8898080, DOI: 10.3233/jad-210041.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseMicroglial functionTREM2 functionTheta-phase gamma-amplitude couplingHippocampal network functionSpontaneous epileptiform seizuresNetwork oscillationsTransgenic AD modelHippocampal neuronal excitabilityMyeloid cells 2Clinical Alzheimer's diseaseWild-type miceHippocampal network oscillationsHippocampal pathophysiologyProgressive dementiaTau pathologyUrethane anesthesiaAD pathophysiologyNeuronal excitabilityEpileptiform seizuresEpileptic activityAD modelTREM2Disease pathologyCells 2AgRP neurons control structure and function of the medial prefrontal cortex
Stutz B, Waterson MJ, Šestan-Peša M, Dietrich MO, Škarica M, Sestan N, Racz B, Magyar A, Sotonyi P, Liu ZW, Gao XB, Matyas F, Stoiljkovic M, Horvath TL. AgRP neurons control structure and function of the medial prefrontal cortex. Molecular Psychiatry 2022, 27: 3951-3960. PMID: 35906488, PMCID: PMC9891653, DOI: 10.1038/s41380-022-01691-8.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAgRP neuronsNon-selective dopamine receptor antagonistBrain functionPrefrontal cortexHypothalamic AgRP neuronsMedial thalamic neuronsAdministration of clozapineDopamine receptor antagonistVentral tegmental areaOscillatory network activityHigher-order brain functionsHypothalamic agoutiThalamic neuronsChemogenetic inhibitionDopaminergic neuronsReceptor antagonistTegmental areaNeuronal pathwaysSensorimotor gatingAdult miceModulatory impactAmbulatory behaviorConstitutive impairmentNeuronsCorrection: Drp1 is required for AgRP neuronal activity and feeding
Jin S, Yoon NA, Liu ZW, Song JE, Horvath TL, Kim JD, Diano S. Correction: Drp1 is required for AgRP neuronal activity and feeding. ELife 2022, 11: e80570. PMID: 35763333, PMCID: PMC9239674, DOI: 10.7554/elife.80570.Peer-Reviewed Original ResearchAgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids
Endle H, Horta G, Stutz B, Muthuraman M, Tegeder I, Schreiber Y, Snodgrass IF, Gurke R, Liu ZW, Sestan-Pesa M, Radyushkin K, Streu N, Fan W, Baumgart J, Li Y, Kloss F, Groppa S, Opel N, Dannlowski U, Grabe HJ, Zipp F, Rácz B, Horvath TL, Nitsch R, Vogt J. AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids. Nature Metabolism 2022, 4: 683-692. PMID: 35760867, PMCID: PMC9940119, DOI: 10.1038/s42255-022-00589-7.Peer-Reviewed Original ResearchConceptsFasting-induced hyperphagiaCortical excitabilityAgRP neuronsLysophosphatidic acidPeripheral metabolismHigher body mass indexFasting-induced elevationHypothalamic AgRP neuronsEffects of LPABody mass indexHigher cortical excitabilityBrain lipid levelsCentral nervous systemPrevalence of typeGlutamatergic transmissionHypothalamic agoutiMass indexOvernight fastingPeptide neuronsCortical synapsesLipid levelsFood intakeCerebrospinal fluidNervous systemPhospholipid levelsPlant mitochondrial FMT and its mammalian homolog CLUH controls development and behavior in Arabidopsis and locomotion in mice
Ralevski A, Apelt F, Olas JJ, Mueller-Roeber B, Rugarli EI, Kragler F, Horvath TL. Plant mitochondrial FMT and its mammalian homolog CLUH controls development and behavior in Arabidopsis and locomotion in mice. Cellular And Molecular Life Sciences 2022, 79: 334. PMID: 35652974, PMCID: PMC11071973, DOI: 10.1007/s00018-022-04382-3.Peer-Reviewed Original ResearchConceptsMitochondrial genesWhole plant morphologySalt stress responseNormal growth conditionsLeaf expansion growthArabidopsis thalianaHigher eukaryotesGene familyMitochondrial proteinsPlant morphologyHomologous functionsMitochondrial morphologyExpansion growthStress responseMitochondrial functionAnimal speciesPlantsSimilar roleGrowth conditionsHeterozygous knockout miceGenesDevelopmental alterationsKnockout miceCLUHArabidopsis