2015
A 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
Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim JG, Suyama S, Koch M, Jin S, Argente-Arizon P, Argente J, Liu ZW, Zimmer MR, Jeong JK, Szigeti-Buck K, Gao Y, Garcia-Caceres C, Yi CX, Salmaso N, Vaccarino FM, Chowen J, Diano S, Dietrich MO, Tschöp MH, Horvath TL. Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nature Neuroscience 2014, 17: 908-910. PMID: 24880214, PMCID: PMC4113214, DOI: 10.1038/nn.3725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCell CountEatingExcitatory Postsynaptic PotentialsGlial Fibrillary Acidic ProteinHypothalamusImmunohistochemistryIn Situ HybridizationLeptinMaleMelanocortinsMiceMice, KnockoutMicroscopy, ElectronNerve NetNeuronsPrimary Cell CulturePro-OpiomelanocortinPulmonary Gas ExchangeReal-Time Polymerase Chain ReactionRNA, MessengerSignal Transduction
2012
Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis
Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Reports 2012, 13: 1079-1086. PMID: 23146889, PMCID: PMC3512417, DOI: 10.1038/embor.2012.174.Peer-Reviewed Original ResearchConceptsGlucose homeostasisEnergy homeostasisPrevalence of obesityWhole-body energy homeostasisBody energy homeostasisAnorectic hormonesAgRP neuronsObese patientsProtein (AgRP) neuronsCentral effectsHypothalamic proopiomelanocortinBody weightInsulin actionLeptinHormonal actionMajor targetInsulin pathwayHomeostasisInsulinNeuronsHormoneBrainLatest findingsEnergy balanceSteady riseLeptin regulates glutamate and glucose transporters in hypothalamic astrocytes
Fuente-Martín E, García-Cáceres C, Granado M, de Ceballos ML, Sánchez-Garrido MÁ, Sarman B, Liu ZW, Dietrich MO, Tena-Sempere M, Argente-Arizón P, Díaz F, Argente J, Horvath TL, Chowen JA. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. Journal Of Clinical Investigation 2012, 122: 3900-3913. PMID: 23064363, PMCID: PMC3484452, DOI: 10.1172/jci64102.Peer-Reviewed Original ResearchConceptsGlial structural proteinsPathology of obesityHypothalamic proopiomelanocortin (POMC) neuronsGlial cell activityOffspring of mothersHigh-fat dietActivity of neuronsExpression of glucoseProopiomelanocortin neuronsHypothalamic astrocytesGlial cellsBody weightSynaptic efficacyGlutamate transportersNeuronal functionCell activityLeptinGlucose uptakeMetabolic statusElectrical activityMetabolic signalsNeuronsAppetiteGlucose transporterKey regulatorFoxO1 Target Gpr17 Activates AgRP Neurons to Regulate Food Intake
Ren H, Orozco IJ, Su Y, Suyama S, Gutiérrez-Juárez R, Horvath TL, Wardlaw SL, Plum L, Arancio O, Accili D. FoxO1 Target Gpr17 Activates AgRP Neurons to Regulate Food Intake. Cell 2012, 149: 1314-1326. PMID: 22682251, PMCID: PMC3613436, DOI: 10.1016/j.cell.2012.04.032.Peer-Reviewed Original ResearchConceptsFood intakeAgRP neuronsG-protein-coupled receptor GPR17Intracerebroventricular injectionHypothalamic neuronsReceptor GPR17Pharmacological modulationGlucose homeostasisNutritional statusTherapeutic potentialMice resultsGenetic ablationNeuronsFoxO1 ablationIntakeSatietyGPR17InsulinExpression profilingAblationPathwayCangrelorObesityLeptinAgonistsGhrelin and the central regulation of feeding and energy balance
Abizaid A, Horvath TL. Ghrelin and the central regulation of feeding and energy balance. Indian Journal Of Endocrinology And Metabolism 2012, 16: 617-626. PMID: 23565498, PMCID: PMC3602992, DOI: 10.4103/2230-8210.105580.Peer-Reviewed Original Research
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
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 basisLeptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding
Leinninger GM, Jo YH, Leshan RL, Louis GW, Yang H, Barrera JG, Wilson H, Opland DM, Faouzi MA, Gong Y, Jones JC, Rhodes CJ, Chua S, Diano S, Horvath TL, Seeley RJ, Becker JB, Münzberg H, Myers MG. Leptin Acts via Leptin Receptor-Expressing Lateral Hypothalamic Neurons to Modulate the Mesolimbic Dopamine System and Suppress Feeding. Cell Metabolism 2009, 10: 89-98. PMID: 19656487, PMCID: PMC2723060, DOI: 10.1016/j.cmet.2009.06.011.Peer-Reviewed Original ResearchConceptsLateral hypothalamic areaVentral tegmental areaMesolimbic DA systemLepRb neuronsMesolimbic dopamine systemLeptin actionLeptin receptorDopamine systemDA systemLeptin-deficient animalsLateral hypothalamic neuronsAnorexigenic hormone leptinLeptin actsHypothalamic areaHypothalamic neuronsSuppress feedingHormone leptinTegmental areaDA contentInhibitory neuronsRate-limiting enzymeBody weightNeuronsLeptinReceptors
2008
Brain circuits regulating energy homeostasis
Abizaid A, Horvath TL. Brain circuits regulating energy homeostasis. Peptides 2008, 149: 3-10. PMID: 18514925, PMCID: PMC2605273, DOI: 10.1016/j.regpep.2007.10.006.Peer-Reviewed Original ResearchCross-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
Anticonvulsant effects of leptin in epilepsy
Diano S, Horvath TL. Anticonvulsant effects of leptin in epilepsy. Journal Of Clinical Investigation 2007, 118: 26-28. PMID: 18097479, PMCID: PMC2147676, DOI: 10.1172/jci34511.Peer-Reviewed Original ResearchMeSH Keywords4-AminopyridineAdministration, IntranasalAlpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidAnimalsConvulsantsHypothalamusJanus Kinase 2LeptinMaleMiceMice, KnockoutNeuronsPentylenetetrazolePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPotassium Channel BlockersPotassium Channels, Voltage-GatedRatsRats, Sprague-DawleyReceptors, AMPAReceptors, LeptinSeizuresSynaptic TransmissionConceptsPeripheral metabolic hormonesTreatment of epilepsyRodent seizure modelsHigher brain functionsAnticonvulsant effectsSeizure modelGlutamate neurotransmissionHormone leptinMetabolic hormonesTherapeutic approachesMetabolic disordersNasal epitheliumLeptinAdipose tissueEpileptic seizuresTherapeutic potentialEnergy homeostasisBrain functionNeuronal processesFat storesEpilepsySeizuresEnergy metabolismCritical regulatorDirect effectEnhanced 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 evidence
2006
Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity
Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Münzberg H, Shanabrough M, Burdakov D, Rother E, Janoschek R, Alber J, Belgardt BF, Koch L, Seibler J, Schwenk F, Fekete C, Suzuki A, Mak TW, Krone W, Horvath TL, Ashcroft FM, Brüning JC. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. Journal Of Clinical Investigation 2006, 116: 1886-1901. PMID: 16794735, PMCID: PMC1481658, DOI: 10.1172/jci27123.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChromonesDietEatingFemaleHypoglycemic AgentsHypothalamusInsulinLeptinMaleMembrane PotentialsMiceMice, KnockoutMorpholinesNeuronsObesityPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoinositide-3 Kinase InhibitorsPotassium ChannelsPro-OpiomelanocortinPTEN PhosphohydrolaseSecond Messenger SystemsTolbutamideConceptsPOMC neuronsATP-sensitive potassium channel activityBasal firing rateHypothalamic proopiomelanocortin (POMC) neuronsElectrical activityKATP channel activationPI3K inhibitor LY294002PTEN knockout micePotassium channel activityK inhibitor LY294002PI3K pathwayProopiomelanocortin neuronsHypothalamic receptorsICV administrationFood intakeKATP channelsKnockout miceMelanocortin systemLeptinFiring rateNeuronsMiceSTAT3 phosphorylationK pathwayInhibitor LY294002Developmental programming of the hypothalamus: a matter of fat
Horvath TL, Bruning JC. Developmental programming of the hypothalamus: a matter of fat. Nature Medicine 2006, 12: 52-53. PMID: 16397567, DOI: 10.1038/nm0106-52.Peer-Reviewed Original Research
2005
Unraveling neuronal circuitry regulating energy homeostasis: Plasticity in feeding circuits
Abizaid A, Horvath T. Unraveling neuronal circuitry regulating energy homeostasis: Plasticity in feeding circuits. Drug Discovery Today Disease Models 2005, 2: 191-196. DOI: 10.1016/j.ddmod.2005.08.009.Peer-Reviewed Original Research
2004
Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, Friedman JM, Horvath TL. Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin. Science 2004, 304: 110-115. PMID: 15064421, DOI: 10.1126/science.1089459.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArcuate Nucleus of HypothalamusBody WeightEatingEvoked PotentialsExcitatory Postsynaptic PotentialsFeeding BehaviorGamma-Aminobutyric AcidGhrelinGlutamic AcidGreen Fluorescent ProteinsIn Vitro TechniquesLeptinLuminescent ProteinsMiceMice, ObeseMice, TransgenicNeuronal PlasticityNeuronsNeuropeptide YPatch-Clamp TechniquesPeptide HormonesPro-OpiomelanocortinRecombinant Fusion ProteinsSynapsesTetrodotoxinTransgenesConceptsProopiomelanocortin neuronsNeuropeptide YFat-derived hormone leptinBehavioral effectsOb/ob miceLeptin-deficient miceOb/obHypothalamic arcuate nucleusWild-type miceNumber of excitatoryArcuate nucleusLeptin effectsPostsynaptic currentsOb miceHormone leptinSynaptic densityInhibitory synapsesFood intakeNeuronal typesLeptinMiceNeuronsFeeding circuitRapid rewiringHours
2002
Leptin Uptake by Serotonergic Neurones of the Dorsal Raphe
Fernández‐Galaz M, Diano S, Horvath TL, Garcia‐Segura L. Leptin Uptake by Serotonergic Neurones of the Dorsal Raphe. Journal Of Neuroendocrinology 2002, 14: 429-434. PMID: 12047717, DOI: 10.1046/j.1365-2826.2002.00783.x.Peer-Reviewed Original ResearchConceptsEffects of leptinRaphe nucleusDorsal rapheFemale ratsMidbrain serotonergic systemsSerotonergic systemSerotonergic neuronesRaphe neuronesDistribution of neuronesMouse recombinant leptinIntracerebroventricular administrationLeptin administrationLeptin uptakeLeptin treatmentPeriventricular grayMale ratsFood intakeRecombinant leptinLeptinSleep patternsGender differencesBrain functionImportant mediatorLeptin accumulationNeurones