2018
Neuronal 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
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 acidsMetabolismActivationObesityAppetiteResponseMolecular and cellular regulation of hypothalamic melanocortin neurons controlling food intake and energy metabolism
Koch M, Horvath TL. Molecular and cellular regulation of hypothalamic melanocortin neurons controlling food intake and energy metabolism. Molecular Psychiatry 2014, 19: 752-761. PMID: 24732669, DOI: 10.1038/mp.2014.30.Peer-Reviewed Original ResearchConceptsHypothalamic melanocortin neuronsEnergy metabolismFood intakePotential functional interactionsMelanocortin neuronsCellular regulationCellular processesFunctional interactionNeuronal circuit activityCellular mechanismsPhysiological behaviorEnergy homeostasisMetabolic eventsRegulationHypothalamic neuronsMetabolic healthObese individualsChronic overloadGlial cellsPhysical activityMetabolic disordersMelanocortin systemNeuronal circuitryCentral connectionsPsychiatric diseases
2012
Loss of Autophagy in Pro-opiomelanocortin Neurons Perturbs Axon Growth and Causes Metabolic Dysregulation
Coupé B, Ishii Y, Dietrich MO, Komatsu M, Horvath TL, Bouret SG. Loss of Autophagy in Pro-opiomelanocortin Neurons Perturbs Axon Growth and Causes Metabolic Dysregulation. Cell Metabolism 2012, 15: 247-255. PMID: 22285542, PMCID: PMC3278575, DOI: 10.1016/j.cmet.2011.12.016.Peer-Reviewed Original ResearchMeSH KeywordsAdiposityAnimalsArcuate Nucleus of HypothalamusAutophagyAutophagy-Related Protein 7AxonsBody WeightGlucose IntoleranceImmunoblottingMetabolic Networks and PathwaysMiceMicroscopy, ElectronMicrotubule-Associated ProteinsNeuronsPro-OpiomelanocortinTranscription Factor TFIIHTranscription FactorsUbiquitinConceptsPOMC neuronsHypothalamic melanocortin systemPathogenesis of obesityImportant intracellular mechanismNormal metabolic regulationP62-positive aggregatesFunctional neural systemsGlucose intoleranceAge-dependent accumulationNeonatal lifeAxonal projectionsMetabolic dysregulationMetabolic impairmentMelanocortin systemEssential autophagy geneBody weightLoss of autophagyMajor negative regulatorAxon growthIntracellular mechanismsNeuronsAutophagy deficiencyNeural developmentDirect genetic evidenceAtg7
2011
Nicotine Decreases Food Intake Through Activation of POMC Neurons
Mineur YS, Abizaid A, Rao Y, Salas R, DiLeone RJ, Gündisch D, Diano S, De Biasi M, Horvath TL, Gao XB, Picciotto MR. Nicotine Decreases Food Intake Through Activation of POMC Neurons. Science 2011, 332: 1330-1332. PMID: 21659607, PMCID: PMC3113664, DOI: 10.1126/science.1201889.Peer-Reviewed Original ResearchConceptsFood intakePOMC neuronsNicotine decreases food intakeDecrease food intakePro-opiomelanocortin (POMC) neuronsΑ3β4 nicotinic acetylcholine receptorsHypothalamic melanocortin systemNicotine-induced decreasesMelanocortin-4 receptorNicotinic acetylcholine receptorsAnorexic effectDecrease appetiteSmoking cessationSynaptic mechanismsMelanocortin systemNovel treatmentsBody weightAcetylcholine receptorsNeurobiological mechanismsNeuronsIntakeSubsequent activationAppetiteActivationReceptors
2010
Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity
Dietrich MO, Antunes C, Geliang G, Liu ZW, Borok E, Nie Y, Xu AW, Souza DO, Gao Q, Diano S, Gao XB, Horvath TL. Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity. Journal Of Neuroscience 2010, 30: 11815-11825. PMID: 20810901, PMCID: PMC2965459, DOI: 10.1523/jneurosci.2234-10.2010.Peer-Reviewed Original ResearchConceptsFood intakeMelanocortin systemAgRP neuronal activityAnorexigenic POMC neuronsHypothalamic melanocortin systemAction of SIRT1Negative energy balanceAgRP neuronsPOMC neuronsCre-lox technologyInhibitory toneMC4R antagonistFat massLean massSynaptic inputsNeuronal activityNeuronal firingAdult miceBody weightSIRT1 inhibitorSynaptic plasticityCalorie restrictionMelanocortin receptorsSIRT1 activityBody metabolismSynaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity
Horvath TL, Sarman B, García-Cáceres C, Enriori PJ, Sotonyi P, Shanabrough M, Borok E, Argente J, Chowen JA, Perez-Tilve D, Pfluger PT, Brönneke HS, Levin BE, Diano S, Cowley MA, Tschöp MH. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 14875-14880. PMID: 20679202, PMCID: PMC2930476, DOI: 10.1073/pnas.1004282107.Peer-Reviewed Original ResearchConceptsHigh-fat dietSynaptic input organizationReactive gliosisPOMC neuronsDIO ratsDR ratsArcuate nucleusMelanocortin systemPOMC cellsNeuropeptide Y cellsInput organizationLoss of synapsesDiet-induced obesityBlood-brain barrierHFD-fed animalsDIO animalsAnorexigenic proopiomelanocortinGlial ensheathmentSynaptic organizationInhibitory inputsLean ratsDR animalsNeuronal circuitsCell bodiesGliosis
2008
Fuel utilization by hypothalamic neurons: roles for ROS
Horvath TL, Andrews ZB, Diano S. Fuel utilization by hypothalamic neurons: roles for ROS. Trends In Endocrinology And Metabolism 2008, 20: 78-87. PMID: 19084428, DOI: 10.1016/j.tem.2008.10.003.Peer-Reviewed Original ResearchConceptsEnergy homeostasisFree radical productionAnorexigenic neuronsNeuronal doctrineArcuate nucleusHypothalamic neuronsHypothalamic outputMelanocortin systemEffect of glucoseNeuronal functionFree radical formationSpecific neuronsAcid levelsNeuronsAmino acid levelsNeurobiological aspectsRadical productionEvidence pointsFatty acidsFuel sensingIntracellular substratesHomeostasisNutritional signalsGlucoseHypothalamus
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 LY294002Ghrelin 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