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 mitochondriaAgRP Neurons Regulate Bone Mass
Kim JG, Sun BH, Dietrich MO, Koch M, Yao GQ, Diano S, Insogna K, Horvath TL. AgRP Neurons Regulate Bone Mass. Cell Reports 2015, 13: 8-14. PMID: 26411686, PMCID: PMC5868421, DOI: 10.1016/j.celrep.2015.08.070.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusBone DensityBone Diseases, MetabolicFemurGene Expression RegulationHomeostasisHypothalamusIon ChannelsLeptinMaleMiceMice, KnockoutMitochondrial ProteinsNeuronsNorepinephrinePhenotypePropranololReceptors, Adrenergic, betaReceptors, LeptinSignal TransductionSirtuin 1TibiaUncoupling Protein 2ConceptsAgRP neuronsCell-autonomous deletionSignificant regulatory roleAgRP neuronal functionBone massLeptin receptor deletionSkeletal bone metabolismTransgenic animalsRegulatory roleGene deletionBone homeostasisDeletionNeuronal functionPostnatal deletionSympathetic toneReceptor deletionArcuate nucleusLeptin actionBone metabolismSkeletal metabolismMultiple linesNeuronsMiceMetabolismCircuit integrity
2009
A 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 ResearchMeSH KeywordsAppetiteBone DensityBrain StemEnergy MetabolismHypothalamusLeptinReceptors, LeptinSerotoninSignal TransductionConceptsSerotonergic 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
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 effect
1999
Synaptic Interaction between Hypocretin (Orexin) and Neuropeptide Y Cells in the Rodent and Primate Hypothalamus: A Novel Circuit Implicated in Metabolic and Endocrine Regulations
Horvath T, Diano S, van den Pol A. Synaptic Interaction between Hypocretin (Orexin) and Neuropeptide Y Cells in the Rodent and Primate Hypothalamus: A Novel Circuit Implicated in Metabolic and Endocrine Regulations. Journal Of Neuroscience 1999, 19: 1072-1087. PMID: 9920670, PMCID: PMC6782143, DOI: 10.1523/jneurosci.19-03-01072.1999.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsChlorocebus aethiopsEndocrine GlandsFemaleHypothalamusIntracellular Signaling Peptides and ProteinsMaleMetabolismNeural PathwaysNeuronsNeuropeptide YNeuropeptidesOrexin ReceptorsOrexinsRatsRats, Sprague-DawleyReceptors, Cell SurfaceReceptors, G-Protein-CoupledReceptors, LeptinReceptors, NeuropeptideSynapsesConceptsHypothalamic functionCentral regulationHypocretin-containing neuronsLateral hypothalamic cellsLeptin receptor immunoreactivityNeuropeptide Y cellsDirect synaptic contactsNeuropeptide Y systemEndocrine regulationEndocrine processesNPY releaseReceptor immunoreactivityExcitatory actionHypocretin cellsSynaptic contactsArcuate nucleusLateral hypothalamusPrimate hypothalamusLeptin receptorSame neuronsHypothalamic cellsSynaptic regulationAdipose tissueHypocretinNPY
1998
Leptin receptors in estrogen receptor-containing neurons of the female rat hypothalamus
Diano S, Kalra S, Sakamoto H, Horvath T. Leptin receptors in estrogen receptor-containing neurons of the female rat hypothalamus. Brain Research 1998, 812: 256-259. PMID: 9813356, DOI: 10.1016/s0006-8993(98)00936-6.Peer-Reviewed Original ResearchConceptsLeptin receptorEstrogen receptorNeuronal perikaryaPeripheral signalsEstrogen receptor-containing neuronsParvicellular paraventricular nucleusReceptor-containing neuronsMedial preoptic areaVentromedial hypothalamic nucleusFemale rat hypothalamusArcuate nucleusHypothalamic nucleiFemale ratsParaventricular nucleusPreoptic areaGonadal functionHypothalamic sectionsPeriventricular regionRat hypothalamusNeuroendocrine mechanismsReceptorsExtensive colocalizationLeptinHypothalamusPerikaryaLeptin Receptor Immunoreactivity is Associated with the Golgi Apparatus of Hypothalamic Neurones and Glial Cells
Diano S, Kalra S, Horvath T. Leptin Receptor Immunoreactivity is Associated with the Golgi Apparatus of Hypothalamic Neurones and Glial Cells. Journal Of Neuroendocrinology 1998, 10: 647-650. PMID: 9744481, DOI: 10.1046/j.1365-2826.1998.00261.x.Peer-Reviewed Original ResearchConceptsLeptin receptor immunoreactivityReceptor immunoreactivityPerikaryal membraneGlial cellsGolgi apparatusHypothalamic neuronesCentral nervous systemDifferent second messenger systemsHypothalamic neuronalPeripheral hormonesDentate gyrusSecond messenger systemsEndocrine functionLeptin receptorHypothalamic cellsNervous systemThyroid axisImmunoreactivityCentral mechanismsLeptinIntracellular mechanismsTrans cisternaeNeuronesMessenger systemsPredominant localization