2006
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschöp MH, Gao XB, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal Of Clinical Investigation 2006, 116: 3229-3239. PMID: 17060947, PMCID: PMC1618869, DOI: 10.1172/jci29867.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAppetiteDopamineFluorescent Antibody TechniqueGhrelinMaleMesencephalonMiceMice, Inbred C57BLMice, KnockoutNeuronsNucleus AccumbensPatch-Clamp TechniquesPeptide HormonesRatsRats, Sprague-DawleyReceptors, GhrelinReceptors, G-Protein-CoupledTime FactorsVentral Tegmental AreaConceptsVentral tegmental areaGHSR-deficient miceGHSR-dependent mannerGut hormone ghrelinDopamine neuronal activityMidbrain dopamine neuronsMesolimbic reward circuitrySynaptic input organizationPeripheral ghrelinRebound feedingVTA administrationOrexigenic effectDopamine turnoverGHSR antagonistDopamine neuronsHypothalamic centersTegmental areaHormone ghrelinNucleus accumbensGhrelinNeuronal activitySynapse formationReward circuitryInput organizationFeeding scheduleSynaptic Plasticity in Energy Balance Regulation
Horvath TL. Synaptic Plasticity in Energy Balance Regulation. Obesity 2006, 14: 228s-233s. PMID: 17021372, DOI: 10.1038/oby.2006.314.Peer-Reviewed Original ResearchConceptsOb/ob miceNumber of excitatoryNeuropeptide YSynaptic plasticityPOMC neuronsOb miceFood intakeBehavioral effectsLeptin receptor-deficient miceRearrangement of synapsesLeptin-deficient miceReceptor-deficient miceHypothalamic arcuate nucleusOb/obEnergy balance regulationWild-type miceInfluences brain functionObserved synaptic plasticityWild-type animalsProopiomelanocortin neuronsAnorexigenic hormonesOrexigenic hormonePost-synaptic densityGlutamate inputsExtrahypothalamic sitesGhrelin controls hippocampal spine synapse density and memory performance
Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, Gaskin FS, Nonaka N, Jaeger LB, Banks WA, Morley JE, Pinto S, Sherwin RS, Xu L, Yamada KA, Sleeman MW, Tschöp MH, Horvath TL. Ghrelin controls hippocampal spine synapse density and memory performance. Nature Neuroscience 2006, 9: 381-388. PMID: 16491079, DOI: 10.1038/nn1656.Peer-Reviewed Original ResearchConceptsHippocampal spine synapse densitySpine synapse densitySpine synapse formationGrowth hormone releaseNovel therapeutic strategiesLong-term potentiationHigher brain functionsEnhanced spatial learningGut hormonesGhrelin administrationHypothalamic actionSynapse densitySpine synapsesCA1 regionHormone releaseNeuropeptide ghrelinGhrelin bindingHippocampal formationTherapeutic strategiesMelanocortin systemGhrelinBrain areasMetabolic controlSynaptic changesSynaptic plasticity
2005
A Novel Growth Hormone Secretagogue-1a Receptor Antagonist That Blocks Ghrelin-Induced Growth Hormone Secretion but Induces Increased Body Weight Gain
Halem HA, Taylor JE, Dong JZ, Shen Y, Datta R, Abizaid A, Diano S, Horvath TL, Culler MD. A Novel Growth Hormone Secretagogue-1a Receptor Antagonist That Blocks Ghrelin-Induced Growth Hormone Secretion but Induces Increased Body Weight Gain. Neuroendocrinology 2005, 81: 339-349. PMID: 16210868, DOI: 10.1159/000088796.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArea Under CurveBehavior, AnimalBinding, CompetitiveBody WeightBrainCell CountCHO CellsCricetinaeCricetulusDose-Response Relationship, DrugDrug InteractionsFeeding BehaviorGhrelinGrowth HormoneHumansImmunohistochemistryIodine IsotopesMaleOncogene Proteins v-fosPeptide HormonesRatsRats, Sprague-DawleyReceptors, GhrelinReceptors, G-Protein-CoupledTime FactorsConceptsDorsal medial hypothalamusGHS-1a receptorGrowth hormone secretionBIM-28163Fos-IRWeight gainGH secretionHormone secretionGrowth hormone secretagogue 1a receptorAntagonist of ghrelinMedial arcuate nucleusAction of ghrelinFos protein immunoreactivityAnti-obesity strategiesBody weight gainGhrelin activationConcomitant administrationGhrelin actionMedial hypothalamusArcuate nucleusReceptor antagonistGhrelin receptorFood intakeProtein immunoreactivityHuman ghrelinObesity and the Neuroendocrine Control of Energy Homeostasis: The Role of Spontaneous Locomotor Activity 1
Castañeda TR, Jürgens H, Wiedmer P, Pfluger P, Diano S, Horvath TL, Tang-Christensen M, Tschöp MH. Obesity and the Neuroendocrine Control of Energy Homeostasis: The Role of Spontaneous Locomotor Activity 1. Journal Of Nutrition 2005, 135: 1314-1319. PMID: 15867332, DOI: 10.1093/jn/135.5.1314.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnergy MetabolismGhrelinHomeostasisHumansMotor ActivityNeurosecretory SystemsObesityPeptide HormonesConceptsSpontaneous physical activityWidespread sedentary lifestylesIntolerable side effectsPrevalence of obesityFat mass accumulationCause of deathUrgent global health threatGlobal health threatSafe therapyFat massPharmacological reductionPhysical activitySedentary lifestyleSide effectsEnergy intakeNeuroendocrine factorsNeuroendocrine controlEnergy homeostasisObesityHealth threatMajor predictorActivity 1Molecular mechanismsLow levelsMajor contributor
2004
Novel analogs of ghrelin: physiological and clinical implications
Halem H, Taylor J, Dong J, Shen Y, Datta R, Abizaid A, Diano S, Horvath T, Zizzari P, Bluet-Pajot M, Epelbaum J, Culler M. Novel analogs of ghrelin: physiological and clinical implications. European Journal Of Endocrinology 2004, 151: s71-s75. PMID: 15339248, DOI: 10.1530/eje.0.151s071.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEatingGhrelinGrowth HormoneHumansMalePeptide HormonesRatsReceptors, GhrelinReceptors, G-Protein-CoupledWeight GainConceptsBIM-28163GH secretionGHS receptorWeight gainNeuronal activationGrowth hormone secretagogue receptorAntagonist of ghrelinAction of ghrelinNormal GH secretionRole of ghrelinStimulation of feedingActivity of ghrelinPotential therapeutic benefitAnalogues of ghrelinNative ghrelinEndogenous ghrelinGhrelin actionGH levelsHypothalamic GHHypothalamic sitesSecretagogue receptorGhrelin receptorFood intakeNormal ratsGhrelin analogsCentral Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats
Tang-Christensen M, Vrang N, Ortmann S, Bidlingmaier M, Horvath TL, Tschöp M. Central Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats. Endocrinology 2004, 145: 4645-4652. PMID: 15231700, DOI: 10.1210/en.2004-0529.Peer-Reviewed Original ResearchConceptsNeuropeptides neuropeptide YFood intakePhysical activityLocomotor activityOrexigenic neuropeptides neuropeptide YCentral administrationSpontaneous physical activitySingle intracerebroventricular injectionMajor etiological factorGH secretagogue receptorSpontaneous locomotor activityOverall locomotor activityDose-dependent mannerNovel peptide hormoneGhrelin injectionIntracerebroventricular injectionHypothalamic neuronsNeuropeptide YSecretagogue receptorEtiological factorsGhrelinHigh doseEndogenous ligandHunger factorAgRPRapid 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
2003
The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis
Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu H, Pinto S, Colmers WF, Cone RD, Horvath TL. The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis. Neuron 2003, 37: 649-661. PMID: 12597862, DOI: 10.1016/s0896-6273(03)00063-1.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsCentral Nervous SystemCorticotropin-Releasing HormoneEnergy MetabolismFemaleGhrelinHomeostasisHypothalamusIn Vitro TechniquesIntercellular Signaling Peptides and ProteinsLuminescent ProteinsMiceMice, KnockoutMice, TransgenicNerve NetNeuronsNeuropeptide YOrgan SpecificityParaventricular Hypothalamic NucleusPatch-Clamp TechniquesPeptide HormonesPresynaptic TerminalsPro-OpiomelanocortinProtein BindingProtein BiosynthesisProteinsRatsConceptsCorticotropin-releasing hormoneNeuropeptide YNPY neuronsHypothalamic circuitsGastrointestinal peptide hormone ghrelinEffects of NPYEnergy homeostasisArcuate NPY neuronsRelease of ghrelinExpression of ghrelinMechanism of actionPeptide hormone ghrelinHypothalamic actionOrexigenic peptideHypothalamic nucleiHormone ghrelinParaventricular nucleusProopiomelanocortin (POMC) productsThird ventricleGhrelinPresynaptic terminalsElectrophysiological recordingsNeuronsHypothalamusHomeostasisGhrelin in hypothalamic regulation of energy balance.
Horvath TL, Diano S, Tschöp M. Ghrelin in hypothalamic regulation of energy balance. Current Topics In Medicinal Chemistry 2003, 3: 921-7. PMID: 12678840, DOI: 10.2174/1568026033452230.Peer-Reviewed Original ResearchGhrelin as a potential anti-obesity target.
Horvath TL, Castañeda T, Tang-Christensen M, Pagotto U, Tschöp MH. Ghrelin as a potential anti-obesity target. Current Pharmaceutical Design 2003, 9: 1383-95. PMID: 12769730, DOI: 10.2174/1381612033454748.Peer-Reviewed Original ResearchConceptsPositive energy balancePotential anti-obesity targetEndogenous growth hormone secretagogueEffective pharmacological treatmentAnti-obesity targetGrowth hormone secretagoguesNumerous target tissuesPeptide hormone ghrelinGhrelin antagonistGhrelin actionPharmacological treatmentHormone ghrelinFood intakeHormone secretagoguesPharmacological approachesGhrelinPleiotropic hormoneFat oxidationNeuroendocrine regulationCompensatory mechanismsEnergy homeostasisBlood streamTarget tissuesExact mechanismObesity
2001
Minireview: ghrelin and the regulation of energy balance--a hypothalamic perspective.
Horvath T, Diano S, Sotonyi P, Heiman M, Tschöp M. Minireview: ghrelin and the regulation of energy balance--a hypothalamic perspective. Endocrinology 2001, 142: 4163-9. PMID: 11564668, DOI: 10.1210/endo.142.10.8490.Peer-Reviewed Original ResearchConceptsGH secretionSynthetic ghrelin receptor agonistEnergy homeostasisGhrelin receptor agonistRole of ghrelinEtiology of obesityLeptin actionReceptor agonistClinical trialsChronic changesCentral regulationNeuroendocrine networkGhrelinNutritional stateEnergy deficitImportant regulatorStomachSecretionRecent findingsHomeostasisMost studiesCachexiaObesityHypothalamusPotential significance