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
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, PMCID: PMC11323787, 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 FAHunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice
Varela L, Stutz B, Song JE, Kim JG, Liu ZW, Gao XB, Horvath TL. Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice. Journal Of Clinical Investigation 2021, 131 PMID: 33848272, PMCID: PMC8121506, DOI: 10.1172/jci144239.Peer-Reviewed Original ResearchConceptsAgRP neuronsHypothalamic feeding circuitsInhibitory neurotransmitter GABAGhrelin administrationInhibitory toneAstrocytic responseMetabolic milieuProstaglandin E2Neurotransmitter GABANeuronal controlSynaptic plasticityGlial processesNeuronsNeural excitationMitochondrial adaptationsFood deprivationAstrocytesPerikaryaFeeding circuitRegion crucialFeedingObesityGABAExcitabilityChemogenetics
2020
Crosstalk between maternal perinatal obesity and offspring dopaminergic circuitry
Yasumoto Y, Horvath TL. Crosstalk between maternal perinatal obesity and offspring dopaminergic circuitry. Journal Of Clinical Investigation 2020, 130: 3416-3418. PMID: 32510474, PMCID: PMC7324168, DOI: 10.1172/jci138123.Peer-Reviewed Original ResearchConceptsMedium spiny neuronsHigh-fat dietMaternal obesityD1 medium spiny neuronsD2 medium spiny neuronsFetal brain developmentDopamine midbrain neuronsBehavioral phenotypesAltered excitatoryPerinatal obesityMaternal miceInhibitory balanceSpiny neuronsDopaminergic circuitryMidbrain neuronsBrain developmentObesityAdult HealthOffspring developmentNeuronsPhenotypeExcitatoryMice
2019
Metabolism: A Burning Opioid Issue in Obesity Therapeutics
da Silva Catarino J, Horvath TL. Metabolism: A Burning Opioid Issue in Obesity Therapeutics. Current Biology 2019, 29: r1323-r1325. PMID: 31846684, DOI: 10.1016/j.cub.2019.10.055.Peer-Reviewed Original Research
2018
Insulin 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 responsesObesityRegulationMechanismPlasticityExpressionFrom white to beige: a new hypothalamic pathway
Miletta MC, Horvath TL. From white to beige: a new hypothalamic pathway. EMBO Reports 2018, 19: embr201845928. PMID: 29581171, PMCID: PMC5891399, DOI: 10.15252/embr.201845928.Peer-Reviewed Original ResearchConceptsVentromedial hypothalamusSympathetic nervous system outflowSubcutaneous white adipose tissueWhite adipose tissueSympathetic outflowHypothalamic pathwaysHomeostatic signalsAdipose tissueBeige fatBeige adipocytesNeuronal circuitsEnergy homeostasisFat tissueSystem outflowNeuronsMetabolic roleTissueActivationCross talkRegulatory pathwaysBeigingObesityHypothalamusVMHPathwayNeuronal Cilia: Another Player in the Melanocortin System
Varela L, Horvath TL. Neuronal Cilia: Another Player in the Melanocortin System. Trends In Molecular Medicine 2018, 24: 333-334. PMID: 29501261, DOI: 10.1016/j.molmed.2018.02.004.Peer-Reviewed Original Research
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 relationshipMiceMacrophagesRegulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1
Rathjen T, Yan X, Kononenko NL, Ku MC, Song K, Ferrarese L, Tarallo V, Puchkov D, Kochlamazashvili G, Brachs S, Varela L, Szigeti-Buck K, Yi CX, Schriever SC, Tattikota SG, Carlo AS, Moroni M, Siemens J, Heuser A, van der Weyden L, Birkenfeld AL, Niendorf T, Poulet JFA, Horvath TL, Tschöp MH, Heinig M, Trajkovski M, Haucke V, Poy MN. Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1. Nature Neuroscience 2017, 20: 1096-1103. PMID: 28628102, PMCID: PMC5533218, DOI: 10.1038/nn.4590.Peer-Reviewed Original Research4.19 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
2016
The role of astrocytes in the hypothalamic response and adaptation to metabolic signals
Chowen JA, Argente-Arizón P, Freire-Regatillo A, Frago LM, Horvath TL, Argente J. The role of astrocytes in the hypothalamic response and adaptation to metabolic signals. Progress In Neurobiology 2016, 144: 68-87. PMID: 27000556, DOI: 10.1016/j.pneurobio.2016.03.001.Peer-Reviewed Original ResearchConceptsHypothalamic responseMetabolic signalsRole of astrocytesIncidence of obesityAnorexigenic hormone leptinType 2 diabetesHypothalamic adaptationsImportant metabolic signalsDiabetes mellitusHypothalamic circuitsSecondary complicationsChronic conditionsHormone leptinGlial cellsSynaptic transmissionAdequate treatmentMetabolic diseasesSynaptic plasticityNeuroendocrine controlHomeostatic functionsNeighboring neuronsMetabolic homeostasisHormonal inputsObesityHypothalamus
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 mitochondriaA Sympathetic View on Fat by Leptin
Varela L, Horvath TL. A Sympathetic View on Fat by Leptin. Cell 2015, 163: 26-27. PMID: 26406366, DOI: 10.1016/j.cell.2015.09.016.Peer-Reviewed Original ResearchThe role of the hypothalamus in the maintenance of energy balance and peripheral glucose control
Varela L, Horvath T. The role of the hypothalamus in the maintenance of energy balance and peripheral glucose control. 2015, 529-537. DOI: 10.1002/9781118387658.ch36.Peer-Reviewed Original ResearchEnergy homeostasisPrevalence of obesityAnorectic hormonesAgRP neuronsHypothalamic POMCObese patientsGlucose controlGlucose homeostasisBody weightInsulin actionHormonal actionLeptinMajor targetInsulinHormoneBrainHomeostasisLatest findingsEnergy balanceSteady riseObesityPatientsHypothalamusPathwayPrevalence
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 acidsMetabolismActivationObesityAppetiteResponseA temperature hypothesis of hypothalamus-driven obesity.
Horvath TL, Stachenfeld NS, Diano S. A temperature hypothesis of hypothalamus-driven obesity. The Yale Journal Of Biology And Medicine 2014, 87: 149-58. PMID: 24910560, PMCID: PMC4031788.Commentaries, Editorials and LettersConceptsTreatment of obesityWhite adipose tissueEtiology of obesityBrain temperature controlHealth care systemSustained obesityObesity developmentPeripheral tissuesMetabolic disordersLarge financial burdenObesityAdipose tissueMedical strategiesExcess fatMetabolic centersPsychological symptomsLength of lifeCare systemFinancial burdenMetabolic stateTissueVast majorityPatientsEtiologySymptomsMinireview: 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
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