2022
Paraventricular glia drive circuit function to control metabolism
Varela L, Horvath TL. Paraventricular glia drive circuit function to control metabolism. Cell Metabolism 2022, 34: 1424-1426. PMID: 36198288, DOI: 10.1016/j.cmet.2022.09.012.Peer-Reviewed Original Research
2021
Drp1 is required for AgRP neuronal activity and feeding
Jin S, Yoon NA, Liu ZW, Song JE, Horvath TL, Kim JD, Diano S. Drp1 is required for AgRP neuronal activity and feeding. ELife 2021, 10: e64351. PMID: 33689681, PMCID: PMC7946429, DOI: 10.7554/elife.64351.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsBody WeightDynaminsEnergy MetabolismFastingFeeding BehaviorFemaleMaleMiceNeuronsConceptsAgRP neuronal activityFatty acid oxidationAgRP neuronsNeuronal activityAgRP neuronal functionHypothalamic AgRP neuronsBody weight regulationMitochondrial fatty acid utilizationWhole-body energy homeostasisHypothalamic orexigenic agoutiFatty acid utilizationAcid oxidationFat massCKO miceNeuronal activationPeptide-1Body weightNeuronal functionOrexigenic agoutiEnergy homeostasisMitochondrial fissionSignificant decreaseEnergy expenditureNeuronsAcid utilizationDefective autophagy in Sf1 neurons perturbs the metabolic response to fasting and causes mitochondrial dysfunction
Coupé B, Leloup C, Asiedu K, Maillard J, Pénicaud L, Horvath TL, Bouret SG. Defective autophagy in Sf1 neurons perturbs the metabolic response to fasting and causes mitochondrial dysfunction. Molecular Metabolism 2021, 47: 101186. PMID: 33571700, PMCID: PMC7907893, DOI: 10.1016/j.molmet.2021.101186.Peer-Reviewed Original ResearchConceptsLoss of Atg7Energy homeostasisCellular homeostasisGene Atg7Defective autophagyMitochondria morphologyPhysiological processesCellular responsesCellular componentsMetabolic responseMitochondrial dysfunctionAutophagyAtg7SF1 neuronsHomeostasisMutant miceNeurons displayLoxP/Energy expenditure regulationImportant roleVMH neuronsVentromedial nucleusLeptin sensitivityStarvationCentral response
2019
Parallel Paths in PVH Control of Feeding
Varela L, Horvath TL. Parallel Paths in PVH Control of Feeding. Neuron 2019, 102: 514-516. PMID: 31071283, DOI: 10.1016/j.neuron.2019.04.026.Peer-Reviewed Original Research
2018
Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
García-Cáceres C, Balland E, Prevot V, Luquet S, Woods SC, Koch M, Horvath TL, Yi CX, Chowen JA, Verkhratsky A, Araque A, Bechmann I, Tschöp MH. Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism. Nature Neuroscience 2018, 22: 7-14. PMID: 30531847, DOI: 10.1038/s41593-018-0286-y.Peer-Reviewed Original ResearchConceptsControl of metabolismNon-neuronal cellsNeuronal-glial networksFunctional interactionSpecific neuronal subpopulationsEnergy metabolismHypothalamic feeding circuitsRole of astrocytesPhysiological responsesGlial-neuronal interactionsMetabolismFood-related cuesNeuronal subpopulationsSystemic metabolismFood intakeBrain controlMetabolic statusRecent advancesMicrogliaAstrocytesGeneticsTanycytesComplex setBiologyInteroceptive signalsMild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity
Timper K, Paeger L, Sánchez-Lasheras C, Varela L, Jais A, Nolte H, Vogt MC, Hausen AC, Heilinger C, Evers N, Pospisilik JA, Penninger JM, Taylor EB, Horvath TL, Kloppenburg P, Brüning JC. Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity. Cell Reports 2018, 25: 383-397.e10. PMID: 30304679, PMCID: PMC6349418, DOI: 10.1016/j.celrep.2018.09.034.Peer-Reviewed Original ResearchConceptsPOMC neuronsApoptosis-inducing factorImproved glucose metabolismFatty acid utilizationDecrease firingPomc-CreFatty acid metabolismHFD feedingReactive oxygen species formationSystemic glucoseHypothalamic proopiomelanocortinLean miceMitochondrial respirationObese miceObese conditionsInsulin sensitivityGlucose homeostasisGlucose metabolismMild impairmentOxygen species formationFiring propertiesNeuronsOxidative phosphorylationMicePartial impairmentViral Vectors for Studying Brain Mechanisms that Control Energy Homeostasis
Mancini G, Horvath TL. Viral Vectors for Studying Brain Mechanisms that Control Energy Homeostasis. Cell Metabolism 2018, 27: 1168-1175. PMID: 29874565, DOI: 10.1016/j.cmet.2018.05.015.Peer-Reviewed Original Research
2017
Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1
Rathjen T, Yan X, Kononenko NL, Ku MC, Song K, Ferrarese L, Tarallo V, Puchkov D, Kochlamazashvili G, Brachs S, Varela L, Szigeti-Buck K, Yi CX, Schriever SC, Tattikota SG, Carlo AS, Moroni M, Siemens J, Heuser A, van der Weyden L, Birkenfeld AL, Niendorf T, Poulet JFA, Horvath TL, Tschöp MH, Heinig M, Trajkovski M, Haucke V, Poy MN. Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1. Nature Neuroscience 2017, 20: 1096-1103. PMID: 28628102, PMCID: PMC5533218, DOI: 10.1038/nn.4590.Peer-Reviewed Original ResearchMitochondria Bioenergetic and Cognitive Functions: The Cannabinoid Link
Mancini G, Horvath TL. Mitochondria Bioenergetic and Cognitive Functions: The Cannabinoid Link. Trends In Cell Biology 2017, 27: 391-392. PMID: 28487182, DOI: 10.1016/j.tcb.2017.04.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCannabinoidsCognitionEnergy MetabolismHumansMitochondriaModels, BiologicalSignal TransductionEndothelial HIF-1α Enables Hypothalamic Glucose Uptake to Drive POMC Neurons
Varela L, Suyama S, Huang Y, Shanabrough M, Tschöp M, Gao XB, Giordano FJ, Horvath TL. Endothelial HIF-1α Enables Hypothalamic Glucose Uptake to Drive POMC Neurons. Diabetes 2017, 66: db161106. PMID: 28292966, PMCID: PMC5440016, DOI: 10.2337/db16-1106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternEndotheliumEnergy MetabolismFood DeprivationGene Knockdown TechniquesGlucoseHyperphagiaHypothalamusHypoxia-Inducible Factor 1, alpha SubunitImmunohistochemistryMiceMicroscopy, ElectronMitochondriaNeuronsPatch-Clamp TechniquesPro-OpiomelanocortinReal-Time Polymerase Chain ReactionConceptsPOMC neuronsGlucose uptakePOMC neuronal activityHypothalamic proopiomelanocortin (POMC) neuronsHypoxia-inducible factor-1αProopiomelanocortin neuronsVascular impairmentGlucose administrationMetabolic disordersNeuronal activityMetabolic environmentFactor-1αImpaired functioningEndothelial cellsNeuronsFood deprivationVivoCentral controlHypothalamusMiceAdministrationUptakeImpairment
2016
CD301b+ Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha
Kumamoto Y, Camporez JP, Jurczak MJ, Shanabrough M, Horvath T, Shulman GI, Iwasaki A. CD301b+ Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha. Immunity 2016, 45: 583-596. PMID: 27566941, PMCID: PMC5033704, DOI: 10.1016/j.immuni.2016.08.002.Peer-Reviewed Original ResearchConceptsMononuclear phagocytesResistin-like molecule αResistin-like molecule alphaSignificant weight lossPositive energy balanceInsulin sensitivityGlucose metabolismAdipose tissueBody weightMultiple organsMultifunctional cytokineBody homeostasisMarked reductionHeterogeneous groupWeight lossPhagocytesMolecule αHomeostasisEnergy balanceRELMαCD301bNormoglycemiaCytokinesMacrophagesHypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis
Jin S, Kim JG, Park JW, Koch M, Horvath TL, Lee BJ. Hypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis. Scientific Reports 2016, 6: 29424. PMID: 27405276, PMCID: PMC4942617, DOI: 10.1038/srep29424.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnorexiaArcuate Nucleus of HypothalamusCyclooxygenase InhibitorsEnergy MetabolismFeverInflammationLipopeptidesMaleMiceMice, KnockoutMicrogliaMyeloid Differentiation Factor 88NF-kappa BPro-OpiomelanocortinRatsReceptor, Melanocortin, Type 3Receptor, Melanocortin, Type 4Toll-Like Receptor 2Weight LossConceptsSickness behaviorHypothalamic inflammationToll-like receptor 2 (TLR2) activationSickness behavior symptomsNuclear factor kappa BBody weight lossReceptor 2 activationFactor kappa BNeuronal circuit functionHypothalamic microgliaProopiomelanocortin neuronsInflammatory mechanismsIntracerebroventricular injectionPathophysiologic mechanismsTLR2 activationInflammatory processCyclooxygenase pathwayNeuronal activationKappa BBehavior symptomsWeight lossInput organizationMicrogliaTLR2Inflammation
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 mitochondriaNeuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding
Waterson MJ, Horvath TL. Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding. Cell Metabolism 2015, 22: 962-970. PMID: 26603190, DOI: 10.1016/j.cmet.2015.09.026.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainEnergy IntakeEnergy MetabolismHumansHypothalamusPituitary GlandReceptors, MelanocortinDevelopmental programming of hypothalamic neuroendocrine systems
Ralevski A, Horvath TL. Developmental programming of hypothalamic neuroendocrine systems. Frontiers In Neuroendocrinology 2015, 39: 52-58. PMID: 26391503, DOI: 10.1016/j.yfrne.2015.09.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnergy MetabolismFemaleFetal DevelopmentHumansHypothalamusNeurosecretory SystemsPregnancyConceptsHypothalamic neuroendocrine systemsDevelopmental programmingNeuroendocrine systemMetabolic fateMetabolic syndromeHypothalamic circuitsPerinatal environmentPossible cognitive impairmentMetabolic programmingCognitive impairmentMetabolic influencesEnergy homeostasisCritical periodNeural systemsSyndromeHypothalamic 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
2014
Hypothalamic Sidedness in Mitochondrial Metabolism
Toth I, Kiss DS, Goszleth G, Bartha T, Frenyo LV, Naftolin F, Horvath TL, Zsarnovszky A. Hypothalamic Sidedness in Mitochondrial Metabolism. Reproductive Sciences 2014, 21: 1492-1498. PMID: 24740989, DOI: 10.1177/1933719114530188.Peer-Reviewed Original ResearchMitochondrial 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 acidsMetabolismActivationObesityAppetiteResponsePPARγ ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding
Long L, Toda C, Jeong JK, Horvath TL, Diano S. PPARγ ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding. Journal Of Clinical Investigation 2014, 124: 4017-4027. PMID: 25083994, PMCID: PMC4151211, DOI: 10.1172/jci76220.Peer-Reviewed Original ResearchConceptsHigh-fat dietPOMC neuronsFood intakeImproved glucose metabolismHigh-fat feedingWhole-body energy balanceBody weight gainProopiomelanocortin neuronsPeripheral administrationFat massLeptin sensitivityControl animalsGlucose metabolismBody weightPPARγ activatorsLocomotor activityEnergy homeostasisPPARγWeight gainNeuronsSelective ablationEnergy expenditureIntakeNuclear receptorsMiceFunction and Dysfunction of Hypocretin/Orexin: An Energetics Point of View
Gao XB, Horvath T. Function and Dysfunction of Hypocretin/Orexin: An Energetics Point of View. Annual Review Of Neuroscience 2014, 37: 101-116. PMID: 24821311, DOI: 10.1146/annurev-neuro-071013-013855.Peer-Reviewed Original Research