2018
Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis
Aryal B, Singh AK, Zhang X, Varela L, Rotllan N, Goedeke L, Chaube B, Camporez JP, Vatner DF, Horvath TL, Shulman GI, Suárez Y, Fernández-Hernando C. Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis. JCI Insight 2018, 3: e97918. PMID: 29563332, PMCID: PMC5926923, DOI: 10.1172/jci.insight.97918.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAllelesAngiopoietin-Like Protein 4AnimalsAtherosclerosisBody WeightChemokinesCytokinesDiet, High-FatDiet, WesternFatty AcidsGene Expression ProfilingGene Expression RegulationGene Knockout TechniquesGlucoseInsulinIntegrasesIntercellular Signaling Peptides and ProteinsLipid MetabolismLipoprotein LipaseLipoproteinsLiverMaleMiceMice, Inbred C57BLMice, KnockoutMusclesObesityProprotein Convertase 9TriglyceridesConceptsAngiopoietin-like protein 4High-fat dietEctopic lipid depositionLipid depositionGlucose toleranceLipoprotein lipaseShort-term high-fat dietSevere metabolic abnormalitiesProgression of atherosclerosisMajor risk factorTriacylglycerol-rich lipoproteinsFatty acid uptakeAdipose tissue resultsProatherogenic lipoproteinsCardiometabolic diseasesMetabolic abnormalitiesKO miceRisk factorsWhole body lipidMetabolic disordersGlucose metabolismLPL activityAdipose tissueGenetic ablationRapid clearance
2017
Endothelial 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
2015
Mitochondria in Control of Hypothalamic Metabolic Circuits
Nasrallah C, Horvath T. Mitochondria in Control of Hypothalamic Metabolic Circuits. 2015, 186-202. DOI: 10.1002/9781119017127.ch8.Peer-Reviewed Original ResearchPOMC neuronsNutritional statusBody nutritional statusAgRP neuronsGhrelin increasesLeptin levelsFood intakeCentral regulationGlucose levelsMetabolic disordersNeuronal functionPrimary siteLipid metabolismMetabolic principlesMitochondrial dysfunctionNeuronsCessation of feedingBioenergetic adaptationImportant contributorMitochondrial dynamicsMetabolic circuitsHypothalamusDysfunctionSatietyIntake
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 acidsMetabolismActivationObesityAppetiteResponseA temperature hypothesis of hypothalamus-driven obesity.
Horvath TL, Stachenfeld NS, Diano S. A temperature hypothesis of hypothalamus-driven obesity. The Yale Journal Of Biology And Medicine 2014, 87: 149-58. PMID: 24910560, PMCID: PMC4031788.Commentaries, Editorials and LettersConceptsTreatment of obesityWhite adipose tissueEtiology of obesityBrain temperature controlHealth care systemSustained obesityObesity developmentPeripheral tissuesMetabolic disordersLarge financial burdenObesityAdipose tissueMedical strategiesExcess fatMetabolic centersPsychological symptomsLength of lifeCare systemFinancial burdenMetabolic stateTissueVast majorityPatientsEtiologySymptomsMolecular 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
Sirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism
Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath TL, Sinclair DA, Pfluger PT, Tschöp MH. Sirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism. Physiological Reviews 2012, 92: 1479-1514. PMID: 22811431, PMCID: PMC3746174, DOI: 10.1152/physrev.00022.2011.Peer-Reviewed Original ResearchConceptsSirtuin 1Sirtuin 3Nonalcoholic fatty liver diseaseMammalian sirtuin 1Multiple metabolic benefitsFatty liver diseaseDiet-induced obesityType 2 diabetesActivation of sirtuinsLiver diseaseCellular energy storesMetabolic benefitsMetabolic disordersPharmacological meansEnergy homeostasisPhysiological modulatorDependent deacetylasesMetabolic processesSirtuinsCellular energy homeostasisEnergy storesCellular sensorsEnergy statusAnabolic processesCatabolic process
2007
Anticonvulsant effects of leptin in epilepsy
Diano S, Horvath TL. Anticonvulsant effects of leptin in epilepsy. Journal Of Clinical Investigation 2007, 118: 26-28. PMID: 18097479, PMCID: PMC2147676, DOI: 10.1172/jci34511.Peer-Reviewed Original ResearchMeSH Keywords4-AminopyridineAdministration, IntranasalAlpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidAnimalsConvulsantsHypothalamusJanus Kinase 2LeptinMaleMiceMice, KnockoutNeuronsPentylenetetrazolePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPotassium Channel BlockersPotassium Channels, Voltage-GatedRatsRats, Sprague-DawleyReceptors, AMPAReceptors, LeptinSeizuresSynaptic TransmissionConceptsPeripheral metabolic hormonesTreatment of epilepsyRodent seizure modelsHigher brain functionsAnticonvulsant effectsSeizure modelGlutamate neurotransmissionHormone leptinMetabolic hormonesTherapeutic approachesMetabolic disordersNasal epitheliumLeptinAdipose tissueEpileptic seizuresTherapeutic potentialEnergy homeostasisBrain functionNeuronal processesFat storesEpilepsySeizuresEnergy metabolismCritical regulatorDirect effect
2006
The unfolding cannabinoid story on energy homeostasis: central or peripheral site of action?
Horvath TL. The unfolding cannabinoid story on energy homeostasis: central or peripheral site of action? International Journal Of Obesity 2006, 30: s30-s32. PMID: 16570102, DOI: 10.1038/sj.ijo.0803275.Peer-Reviewed Original ResearchConceptsBlood-brain barrierCB1 receptor antagonistCentral endocannabinoid systemBody weight regulationWhite adipose tissueCentral nervous systemMesolimbic reward circuitryObserved beneficial effectsEnergy metabolism regulationAnorectic effectPeripheral actionsReceptor antagonistEndocannabinoid systemCB1 antagonistCB1 receptorsBrain sitesCannabinoid actionFood intakeHuman trialsPeripheral tissuesMetabolic disordersWeight regulationAdipose tissueNervous systemPharmaceutical approaches
2005
The hardship of obesity: a soft-wired hypothalamus
Horvath TL. The hardship of obesity: a soft-wired hypothalamus. Nature Neuroscience 2005, 8: 561-565. PMID: 15856063, DOI: 10.1038/nn1453.Peer-Reviewed Original ResearchConceptsFood intakeMetabolic disordersEnergy expenditureHumoral responseHomeostatic feedback loopSynaptic plasticityBrain circuitryObesityCentral therapyMetabolic phenotypeCellular mechanismsBrain anatomyMetabolic cuesIntakeDisordersCurrent knowledgeMajor advancesHeavy tollMorbidityDiabetesHypothalamusTherapyCNSMortalityMetabolic processes
2004
The floating blueprint of hypothalamic feeding circuits
Horvath TL, Diano S. The floating blueprint of hypothalamic feeding circuits. Nature Reviews Neuroscience 2004, 5: 662-667. PMID: 15263896, DOI: 10.1038/nrn1479.Peer-Reviewed Original ResearchConceptsHypothalamic feeding circuitsNew therapeutic avenuesMetabolic parametersFood intakeMetabolic disordersSynaptic plasticityTherapeutic avenuesLesion studiesGenetic findingsEnergy expenditureEarlier lesion studiesCircuit changesHypothalamusImportant regulatorUnexpected findingMetabolism regulationFeeding circuitFindingsIntakeAppetite
2000
Mitochondrial Uncoupling Protein 2 (UCP2) in the Nonhuman Primate Brain and Pituitary*This work was supported by NSF Grant IBN-9728581, NIH Grants NS-36111, MH-59847, RR-00163, HD-29186, and HD-37186.
Diano S, Urbanski H, Horvath B, Bechmann I, Kagiya A, Nemeth G, Naftolin F, Warden C, Horvath T. Mitochondrial Uncoupling Protein 2 (UCP2) in the Nonhuman Primate Brain and Pituitary*This work was supported by NSF Grant IBN-9728581, NIH Grants NS-36111, MH-59847, RR-00163, HD-29186, and HD-37186. Endocrinology 2000, 141: 4226-4238. PMID: 11089557, DOI: 10.1210/endo.141.11.7740.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain ChemistryChlorocebus aethiopsCorticotropin-Releasing HormoneGene ExpressionHypothalamusImmunohistochemistryIn Situ HybridizationIon ChannelsLimbic SystemMacaca fascicularisMacaca mulattaMembrane Transport ProteinsMicroscopy, FluorescenceMitochondrial ProteinsNeuropeptide YOxytocinPituitary GlandPituitary Gland, AnteriorPituitary Gland, PosteriorProteinsRNA, MessengerUncoupling Protein 2VasopressinsConceptsUncoupling protein 2Pituitary glandAnterior lobePrimate brainAxonal processesBrain stem regionsNonhuman primate brainSitu hybridization histochemistryMessenger RNACentral autonomicRR-00163Mitochondrial uncoupling protein 2Neuropeptide YPrimate hypothalamusAnterior pituitaryMetabolic disordersRodent brainPosterior lobeHybridization histochemistryPOMC cellsCell bodiesUCP2 expressionRodent dataNovel targetBrain