2021
Astrocytic lipid metabolism determines susceptibility to diet-induced obesity
Varela L, Kim JG, Fernández-Tussy P, Aryal B, Liu ZW, Fernández-Hernando C, Horvath TL. Astrocytic lipid metabolism determines susceptibility to diet-induced obesity. Science Advances 2021, 7: eabj2814. PMID: 34890239, PMCID: PMC11323787, DOI: 10.1126/sciadv.abj2814.Peer-Reviewed Original ResearchDiet-induced obesityHypothalamic astrocytesPeroxisome proliferator-activated receptor gammaHypothalamic neuronal circuitsProliferator-activated receptor gammaControl of feedingFatty acid homeostasisSystemic glucoseMetabolic milieuGlucose homeostasisBody weightReceptor gammaSynaptic plasticityNeuronal circuitsNutrient sensingLipid metabolismCellular adaptationObesityAstrocytesAcid homeostasisUnidentified roleFA metabolismEnergy metabolismElevated susceptibilityAvailability of FAHunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice
Varela L, Stutz B, Song JE, Kim JG, Liu ZW, Gao XB, Horvath TL. Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice. Journal Of Clinical Investigation 2021, 131 PMID: 33848272, PMCID: PMC8121506, DOI: 10.1172/jci144239.Peer-Reviewed Original ResearchConceptsAgRP neuronsHypothalamic feeding circuitsInhibitory neurotransmitter GABAGhrelin administrationInhibitory toneAstrocytic responseMetabolic milieuProstaglandin E2Neurotransmitter GABANeuronal controlSynaptic plasticityGlial processesNeuronsNeural excitationMitochondrial adaptationsFood deprivationAstrocytesPerikaryaFeeding circuitRegion crucialFeedingObesityGABAExcitabilityChemogeneticsObesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension
Gruber T, Pan C, Contreras RE, Wiedemann T, Morgan DA, Skowronski AA, Lefort S, De Bernardis Murat C, Le Thuc O, Legutko B, Ruiz-Ojeda FJ, de la Fuente-Fernández M, García-Villalón AL, González-Hedström D, Huber M, Szigeti-Buck K, Müller TD, Ussar S, Pfluger P, Woods SC, Ertürk A, LeDuc CA, Rahmouni K, Granado M, Horvath TL, Tschöp MH, García-Cáceres C. Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension. Cell Metabolism 2021, 33: 1155-1170.e10. PMID: 33951475, PMCID: PMC8183500, DOI: 10.1016/j.cmet.2021.04.007.Peer-Reviewed Original ResearchConceptsBlood pressureObesity-associated increaseObesity-induced hypertensionElevated blood pressureSystemic blood pressureEndothelial growth factorHIF1α-VEGFArterial hypertensionNovel mechanistic linkSympathetic hyperactivityHemodynamic homeostasisHypothalamic astrocytesMetabolic syndromeRegion-specific lossMacrovascular systemsLeptin signalingBrain centersPathophysiological processesHypertensionGliovascular interfacePathway disruptionGrowth factorAstrocytesMechanistic linkAngiopathy
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 signals
2014
Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim JG, Suyama S, Koch M, Jin S, Argente-Arizon P, Argente J, Liu ZW, Zimmer MR, Jeong JK, Szigeti-Buck K, Gao Y, Garcia-Caceres C, Yi CX, Salmaso N, Vaccarino FM, Chowen J, Diano S, Dietrich MO, Tschöp MH, Horvath TL. Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nature Neuroscience 2014, 17: 908-910. PMID: 24880214, PMCID: PMC4113214, DOI: 10.1038/nn.3725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCell CountEatingExcitatory Postsynaptic PotentialsGlial Fibrillary Acidic ProteinHypothalamusImmunohistochemistryIn Situ HybridizationLeptinMaleMelanocortinsMiceMice, KnockoutMicroscopy, ElectronNerve NetNeuronsPrimary Cell CulturePro-OpiomelanocortinPulmonary Gas ExchangeReal-Time Polymerase Chain ReactionRNA, MessengerSignal Transduction
1998
Kainate Glutamate Receptors (GluR5–7) in the Rat Arcuate Nucleus: Relationship to Tanycytes, Astrocytes, Neurons and Gonadal Steroid Receptors
Diano S, Naftolin F, Horvath T. Kainate Glutamate Receptors (GluR5–7) in the Rat Arcuate Nucleus: Relationship to Tanycytes, Astrocytes, Neurons and Gonadal Steroid Receptors. Journal Of Neuroendocrinology 1998, 10: 239-247. PMID: 9630393, DOI: 10.1046/j.1365-2826.1998.00195.x.Peer-Reviewed Original ResearchConceptsGonadal steroid receptorsKainate glutamate receptorsArcuate nucleusGlutamate receptorsKainate receptorsSteroid receptorsGlutamate actionAndrogen receptorGlial elementsMorphological synaptic plasticityNeuro-glial interactionsRat arcuate nucleusIonotropic glutamate receptorsElectron microscopic immunocytochemistrySame perikaryaGonadal steroidsExcitatory neurotransmissionSynaptic plasticityMicroscopic immunocytochemistryReceptorsNeuronsCell populationsDouble labelHormone regulationAstrocytes