2022
Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity
Wang Q, Zhang B, Stutz B, Liu ZW, Horvath TL, Yang X. Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity. Science Advances 2022, 8: eabn8092. PMID: 36044565, PMCID: PMC9432828, DOI: 10.1126/sciadv.abn8092.Peer-Reviewed Original ResearchConceptsVentromedial hypothalamusWhite adipose tissueVMH neuronsAdipose tissueBody weightLipid metabolismRapid weight gainCounterregulatory responsesSympathetic activitySympathetic innervationAdipocyte hypertrophyTissue lipolysisNeuronal excitabilityFood intakePhysical activityObesity phenotypesGenetic ablationWeight gainHomeostatic set pointEnergy expenditureNeuronsInnervationLipolysisSignificant changesCellular sensors
2021
Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10: e66522. PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/elife.66522.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietCoronavirus infectionAged miceT cellsHigher systemic inflammationInfected aged miceCOVID-19 severityCOVID-19 infectionActivation of ketogenesisMouse hepatitis virus strain A59Systemic inflammationInflammatory damageInfluenza infectionClinical hallmarkNLRP3 inflammasomeImmune surveillanceAdipose tissuePotential treatmentInfectionMiceStrongest predictorLungMortalityAge
2019
Mitofusin 2 in Mature Adipocytes Controls Adiposity and Body Weight
Mancini G, Pirruccio K, Yang X, Blücher M, Rodeheffer M, Horvath TL. Mitofusin 2 in Mature Adipocytes Controls Adiposity and Body Weight. Cell Reports 2019, 26: 2849-2858.e4. PMID: 30865877, PMCID: PMC6876693, DOI: 10.1016/j.celrep.2019.02.039.Peer-Reviewed Original ResearchConceptsKnockout miceBody weightMitochondria-endoplasmic reticulum interactionSystemic metabolic dysregulationImpaired glucose metabolismHigh-fat dietObese human subjectsCalorie-dense foodsMitofusin 2Control miceStandard chowLean controlsMetabolic dysregulationFood intakeAdult miceGlucose metabolismStandard dietAdipose tissueBrown fatGlucose utilizationAdiposityTissue levelsSystemic levelsMiceAdult animals
2018
Myeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high-fat diets
Kim KE, Jeong EA, Lee JY, Yi CO, Park KA, Jin Z, Lee JE, Horvath TL, Roh GS. Myeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high-fat diets. Biochemical And Biophysical Research Communications 2018, 499: 1025-1031. PMID: 29634925, DOI: 10.1016/j.bbrc.2018.04.044.Peer-Reviewed Original ResearchConceptsSirt1 KO miceHigh-fat dietInsulin resistanceKO miceLipocalin-2Inflammation-induced insulin resistanceObesity-associated insulin resistanceAnti-inflammatory effectsPrecursor protein levelsWild-type miceHippocampal inflammationWT miceMacrophage infiltrationObese miceLCN2 expressionSIRT1 knockoutType miceHFDAdipose tissueMiceProtein levelsNeuroinflammationSIRT1DietDeficiencyBrown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis
Singh AK, Aryal B, Chaube B, Rotllan N, Varela L, Horvath TL, Suárez Y, Fernández-Hernando C. Brown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis. Molecular Metabolism 2018, 11: 59-69. PMID: 29627378, PMCID: PMC6001401, DOI: 10.1016/j.molmet.2018.03.011.Peer-Reviewed Original ResearchConceptsBrown adipose tissueAdipose tissueAbsence of ANGPTL4Lipoprotein metabolismLPL activityShort-term HFD feedingTriglyceride-rich lipoprotein catabolismLipoprotein lipaseRole of ANGPTL4Novel mouse modelAcute cold exposureGlucose toleranceHFD feedingFatty acidsLipoprotein catabolismWhole body lipidGlucose homeostasisMouse modelGlucose metabolismTAG clearanceBAT resultsLipid metabolismANGPTL4Cold exposureFA oxidationFrom white to beige: a new hypothalamic pathway
Miletta MC, Horvath TL. From white to beige: a new hypothalamic pathway. EMBO Reports 2018, 19 PMID: 29581171, PMCID: PMC5891399, DOI: 10.15252/embr.201845928.Peer-Reviewed Original ResearchConceptsVentromedial hypothalamusSympathetic nervous system outflowSubcutaneous white adipose tissueWhite adipose tissueSympathetic outflowHypothalamic pathwaysHomeostatic signalsAdipose tissueBeige fatBeige adipocytesNeuronal circuitsEnergy homeostasisFat tissueSystem outflowNeuronsMetabolic roleTissueActivationCross talkRegulatory pathwaysBeigingObesityHypothalamusVMHPathwayAbsence 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
Cannabis in fat: high hopes to treat obesity
Hawkins MN, Horvath TL. Cannabis in fat: high hopes to treat obesity. Journal Of Clinical Investigation 2017, 127: 3918-3920. PMID: 29035279, PMCID: PMC5663345, DOI: 10.1172/jci97042.Peer-Reviewed Original ResearchConceptsCannabinoid receptor type 1Body weightNovel peripheral targetsReduced body weightSystemic metabolic changesAdipocyte-specific deletionReceptor type 1Sympathetic toneTotal adiposityCNS effectsPeripheral mechanismsSystemic metabolismPeripheral targetsAdipocyte physiologyAdipose tissueType 1Metabolic changesMetabolic profileEnergy metabolismMetabolismAdiposityObesityCausal relationshipMiceMacrophages
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 balanceRELMαCD301bNormoglycemiaCytokinesMacrophages
2014
O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat
Ruan HB, Dietrich MO, Liu ZW, Zimmer MR, Li MD, Singh JP, Zhang K, Yin R, Wu J, Horvath TL, Yang X. O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat. Cell 2014, 159: 306-317. PMID: 25303527, PMCID: PMC4509746, DOI: 10.1016/j.cell.2014.09.010.Peer-Reviewed Original ResearchConceptsAgRP neuronsFundamental cellular processesWhite fatN-acetylglucosamine (O-GlcNAc) modificationOrexigenic AgRP neuronsVoltage-dependent potassium channelsCellular processesGlcNAc transferaseDynamic physiological processesNuclear proteinsWhite adipose tissue browningPhysiological processesAdipose tissue browningDiet-induced obesityPhysiological relevanceTissue browningGenetic ablationBeige cellsEnergy metabolismInsulin resistanceNeuronal excitabilityPotassium channelsAdipose tissueCentral mechanismsNeuronsA 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 majorityPatientsEtiologySymptoms
2010
Regulatory T cells in obesity: the leptin connection
Matarese G, Procaccini C, De Rosa V, Horvath TL, La Cava A. Regulatory T cells in obesity: the leptin connection. Trends In Molecular Medicine 2010, 16: 247-256. PMID: 20493774, DOI: 10.1016/j.molmed.2010.04.002.Peer-Reviewed Original ResearchConceptsTreg cellsResident Treg cellsRegulatory T cellsAdipocyte-derived hormonePathogenesis of obesityT cell responsivenessChronic inflammationHypothalamic levelT cellsFood intakeCell responsivenessGlucose homeostasisAdipose tissueTherapeutic interventionsNutritional statusObesityRecent findingsCellsTissueMetabolismInflammationLeptinPathogenesisHormoneIntakeUncoupling Protein-2 Decreases the Lipogenic Actions of Ghrelin
Andrews ZB, Erion DM, Beiler R, Choi CS, Shulman GI, Horvath TL. Uncoupling Protein-2 Decreases the Lipogenic Actions of Ghrelin. Endocrinology 2010, 151: 2078-2086. PMID: 20189996, PMCID: PMC2869261, DOI: 10.1210/en.2009-0850.Peer-Reviewed Original ResearchConceptsBody weight gainGhrelin treatmentWeight gainLipogenic actionsBody weightFat oxidationFat metabolismChronic ghrelin treatmentDaily ip injectionsWhite adipose tissueNegative energy balanceCalorie restriction modelOsmotic minipumpsIP injectionBody fatGhrelinAdipose tissueMiceReactive oxygen speciesExact mechanismUCP2 mRNALipogenesisProtein 2Oxygen speciesTreatment
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 effectEnhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation
Plum L, Rother E, Münzberg H, Wunderlich FT, Morgan DA, Hampel B, Shanabrough M, Janoschek R, Könner AC, Alber J, Suzuki A, Krone W, Horvath TL, Rahmouni K, Brüning JC. Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation. Cell Metabolism 2007, 6: 431-445. PMID: 18054313, DOI: 10.1016/j.cmet.2007.10.012.Peer-Reviewed Original ResearchConceptsWhite adipose tissueSympathetic nerve activityBrown adipose tissuePI3k activationAdipose tissueLeptin-deficient ob/obOb/ob miceUnaltered body weightEnergy expenditureOb/obLeptin-sensitive neuronsNerve activityEndogenous leptinOb miceBody weightUCP1 expressionWAT morphologyEnergy homeostasisLeptinSkeletal muscleMicePTEN ablationSignaling pathwaysMitochondrial contentDirect genetic evidence
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
2003
Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator and neuroprotector
Horvath TL, Diano S, Barnstable C. Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator and neuroprotector. Biochemical Pharmacology 2003, 65: 1917-1921. PMID: 12787871, DOI: 10.1016/s0006-2952(03)00143-6.Peer-Reviewed Original ResearchConceptsMitochondrial membrane potentialInner membraneRole of UCP2Normal neuronal functionDiverse tissuesUnknown functionProtein 2Functional significanceImportant playersCentral nervous systemNeuronal functionProteinMembrane potentialNervous systemUCP2Disease statesUCPBrown adipose tissueNew avenuesMitochondriaTissueAdipose tissueUCP1Better understandingUncoupler
1999
Synaptic Interaction between Hypocretin (Orexin) and Neuropeptide Y Cells in the Rodent and Primate Hypothalamus: A Novel Circuit Implicated in Metabolic and Endocrine Regulations
Horvath T, Diano S, van den Pol A. Synaptic Interaction between Hypocretin (Orexin) and Neuropeptide Y Cells in the Rodent and Primate Hypothalamus: A Novel Circuit Implicated in Metabolic and Endocrine Regulations. Journal Of Neuroscience 1999, 19: 1072-1087. PMID: 9920670, PMCID: PMC6782143, DOI: 10.1523/jneurosci.19-03-01072.1999.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsChlorocebus aethiopsEndocrine GlandsFemaleHypothalamusIntracellular Signaling Peptides and ProteinsMaleMetabolismNeural PathwaysNeuronsNeuropeptide YNeuropeptidesOrexin ReceptorsOrexinsRatsRats, Sprague-DawleyReceptors, Cell SurfaceReceptors, G-Protein-CoupledReceptors, LeptinReceptors, NeuropeptideSynapsesConceptsHypothalamic functionCentral regulationHypocretin-containing neuronsLateral hypothalamic cellsLeptin receptor immunoreactivityNeuropeptide Y cellsDirect synaptic contactsNeuropeptide Y systemEndocrine regulationEndocrine processesNPY releaseReceptor immunoreactivityExcitatory actionHypocretin cellsSynaptic contactsArcuate nucleusLateral hypothalamusPrimate hypothalamusLeptin receptorSame neuronsHypothalamic cellsSynaptic regulationAdipose tissueHypocretinNPY