2017
Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons
Suyama S, Ralevski A, Liu ZW, Dietrich MO, Yada T, Simonds SE, Cowley MA, Gao XB, Diano S, Horvath TL. Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons. ELife 2017, 6: e25755. PMID: 28762946, PMCID: PMC5538821, DOI: 10.7554/elife.25755.Peer-Reviewed Original ResearchConceptsExcitatory postsynaptic currentsPOMC neuronsCP-AMPARsFasted stateAMPAR-mediated excitatory postsynaptic currentsCalcium-permeable AMPA glutamate receptorsInhibition of EPSCsHigh-fat diet exposurePOMC neuronal activityPro-opiomelanocortin (POMC) neuronsCalcium-permeable AMPARsElevated leptin levelsAMPA glutamate receptorsAmplitude of mEPSCsFood deprivationEntry of calciumAMPA receptor complexesDiet exposureLeptin levelsPostsynaptic currentsEPSC amplitudeGlutamate receptorsNeuronal activityExtracellular calciumLinear current-voltage relationship
2015
Hypothalamic POMC neurons promote cannabinoid-induced feeding
Koch M, Varela L, Kim JG, Kim JD, Hernández-Nuño F, Simonds SE, Castorena CM, Vianna CR, Elmquist JK, Morozov YM, Rakic P, Bechmann I, Cowley MA, Szigeti-Buck K, Dietrich MO, Gao XB, Diano S, Horvath TL. Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature 2015, 519: 45-50. PMID: 25707796, PMCID: PMC4496586, DOI: 10.1038/nature14260.Peer-Reviewed Original ResearchConceptsPOMC neuronsΒ-endorphinHypothalamic pro-opiomelanocortin (POMC) neuronsOpioid peptide β-endorphinHypothalamic POMC neuronsPromotion of feedingPro-opiomelanocortin (POMC) neuronsCannabinoid receptor 1CB1R activityPOMC activitySated miceHormone releaseHypothalamic administrationFood intakeCentral regulationNeuronal activityParadoxical increaseCB1RReceptor 1POMC cellsNeuronsMitochondrial adaptationsDecreased activityPOMC geneUnsuspected role
2013
Mitochondrial Dynamics Controlled by Mitofusins Regulate Agrp Neuronal Activity and Diet-Induced Obesity
Dietrich MO, Liu ZW, Horvath TL. Mitochondrial Dynamics Controlled by Mitofusins Regulate Agrp Neuronal Activity and Diet-Induced Obesity. Cell 2013, 155: 188-199. PMID: 24074868, PMCID: PMC4142434, DOI: 10.1016/j.cell.2013.09.004.Peer-Reviewed Original ResearchConceptsMitochondrial dynamicsEnergy metabolismCell-type specificCellular energy metabolismWhole-body energy metabolismKey organellesMitofusin 1Mitofusin 2High-fat dietMitochondria sizeAgRP neuronsMfn1Anorexigenic pro-opiomelanocortin (POMC) neuronsAgRP neuronal activityKnockout miceMetabolismPro-opiomelanocortin (POMC) neuronsFusion mechanismDiet-Induced ObesityMitofusinsOverfed stateImportant roleCellsDynamic changesOrganellesMitofusin 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
2012
Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons
Dietrich MO, Horvath TL. Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons. Nature Reviews Drug Discovery 2012, 11: 675-691. PMID: 22858652, DOI: 10.1038/nrd3739.Peer-Reviewed Original ResearchConceptsNPY/AgRP neuronsNegative energy balanceSevere side effectsAgRP neuronsPOMC neuronsPositive energy balanceChronic disordersPeripheral tissuesReactive oxygen speciesSide effectsLong-term positive energy balanceCalorie restrictionAnti-obesity drug developmentBehavioral interventionsIntense behavioral interventionsPro-opiomelanocortin (POMC) neuronsChronic metabolic disorderLong-term treatmentWhite adipose tissueAlternative therapeutic approachAnti-obesity therapiesPromotion of satietyNew drug therapiesPopulations of neuronsHigher brain functions
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
2009
Nesfatin-1-Regulated Oxytocinergic Signaling in the Paraventricular Nucleus Causes Anorexia through a Leptin-Independent Melanocortin Pathway
Maejima Y, Sedbazar U, Suyama S, Kohno D, Onaka T, Takano E, Yoshida N, Koike M, Uchiyama Y, Fujiwara K, Yashiro T, Horvath TL, Dietrich MO, Tanaka S, Dezaki K, Oh-I S, Hashimoto K, Shimizu H, Nakata M, Mori M, Yada T. Nesfatin-1-Regulated Oxytocinergic Signaling in the Paraventricular Nucleus Causes Anorexia through a Leptin-Independent Melanocortin Pathway. Cell Metabolism 2009, 10: 355-365. PMID: 19883614, DOI: 10.1016/j.cmet.2009.09.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnorexiaAutocrine CommunicationCalcium-Binding ProteinsDNA-Binding ProteinsLeptinMelanocortinsMiceNerve Tissue ProteinsNeuroendocrine CellsNucleobindinsOxytocinParacrine CommunicationParaventricular Hypothalamic NucleusPro-OpiomelanocortinRatsRats, ZuckerSignal TransductionSolitary NucleusConceptsNucleus tractus solitariusNesfatin-1Oxytocin releaseParacrine/autocrine actionsNesfatin-1 neuronsParaventricular nucleus functionPro-opiomelanocortin (POMC) neuronsZucker fatty ratsOxytocin receptor antagonistOxytocin terminalsPVN neuronsTractus solitariusReceptor antagonistCentral injectionParaventricular nucleusAutocrine actionMelanocortin pathwayNeuronal activityNeural pathwaysPVNAnorexiaNeuronsNucleus functionOxytocinImmunoelectron micrographs
1992
GABAergic and catecholaminergic innervation of mediobasal hypothalamic β-endorphin cells projecting to the medial preoptic area
Horvath TL, Naftolin F, Leranth C. GABAergic and catecholaminergic innervation of mediobasal hypothalamic β-endorphin cells projecting to the medial preoptic area. Neuroscience 1992, 51: 391-399. PMID: 1281529, DOI: 10.1016/0306-4522(92)90323-t.Peer-Reviewed Original ResearchConceptsMedial preoptic areaPreoptic areaHormone-producing cellsArcuate nucleusHypothalamic beta-endorphin neuronsHormone-releasing hormone (LHRH) neuronsBeta-endorphin neuronsDirect estrogen actionHormone-containing neuronsVentromedial arcuate nucleusRetrograde tracer horseradish peroxidasePro-opiomelanocortin (POMC) neuronsCellular estrogen receptorsPro-opiomelanocortin cellsTracer horseradish peroxidaseΒ-endorphin cellsHormone neuronsImmunoreactive neuronsCatecholaminergic innervationCatecholaminergic neuronsRetrograde tracingSynaptic contactsEstrogen actionCatecholamine fibersAxon terminals