2018
Effects of myeloid sirtuin 1 deficiency on hypothalamic neurogranin in mice fed a high-fat diet
Kim KE, Jeong EA, Shin HJ, Lee JY, Choi EB, An HS, Park KA, Jin Z, Lee DK, Horvath TL, Roh GS. Effects of myeloid sirtuin 1 deficiency on hypothalamic neurogranin in mice fed a high-fat diet. Biochemical And Biophysical Research Communications 2018, 508: 123-129. PMID: 30471862, DOI: 10.1016/j.bbrc.2018.11.126.Peer-Reviewed Original ResearchConceptsHigh-fat dietHypothalamic inflammationSIRT1 deletionWT miceInsulin resistanceKO miceFood intakeNeurogranin expressionParvalbumin protein levelsSIRT1 knockout miceAnorexigenic proopiomelanocortinArcuate nucleusVentromedial hypothalamusHigher food intakeHFDKnockout miceLow expressionMiceWeight gainInflammationProtein levelsNeurograninHypothalamusIntakeDietMyeloid 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 levelsNeuroinflammationSIRT1DietDeficiency
2016
Hypothalamic 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
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease
Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D'Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nature Medicine 2015, 21: 263-269. PMID: 25686106, PMCID: PMC4352123, DOI: 10.1038/nm.3804.Peer-Reviewed Original Research
2013
Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses
Matarese G, Procaccini C, Menale C, Kim JG, Kim JD, Diano S, Diano N, De Rosa V, Dietrich MO, Horvath TL. Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 6193-6198. PMID: 23530205, PMCID: PMC3625304, DOI: 10.1073/pnas.1210644110.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAllelesAnimalsAntigensAutoimmunityCatalytic DomainEncephalomyelitis, Autoimmune, ExperimentalFlow CytometryFood DeprivationForkhead Transcription FactorsGenetic Predisposition to DiseaseHumansHungerHypothalamusInflammationMiceMice, KnockoutMice, TransgenicMyelin SheathNeuronsSirtuin 1Thymus GlandT-Lymphocytes, RegulatoryConceptsRegulatory T cell responsesDelayed-type hypersensitivity responseHypothalamic feeding circuitsPeptide-expressing neuronsRegulatory T cellsSympathetic nervous systemT cell responsesForkhead box P3T helper 1Adaptive immune responsesWhole-body energy metabolismLow energy availabilityT cell activationAutoimmune disease susceptibilityBox P3Hypothalamic agoutiThymic generationHelper 1Hypersensitivity responseProinflammatory cytokinesHypothalamic neuronsSuppressive capacityT cellsImmune responseNervous system
2011
Obesity is associated with hypothalamic injury in rodents and humans
Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW. Obesity is associated with hypothalamic injury in rodents and humans. Journal Of Clinical Investigation 2011, 122: 153-162. PMID: 22201683, PMCID: PMC3248304, DOI: 10.1172/jci59660.Peer-Reviewed Original ResearchConceptsHigh-fat dietHFD feedingMediobasal hypothalamusPeripheral tissuesRodent modelsBody weight controlHypothalamic arcuate nucleusSubstantial weight gainConsequences of obesityNeuron injuryHypothalamic injuryNeuronal injuryNeuroprotective mechanismsReactive gliosisObese humansHypothalamic areaArcuate nucleusInflammatory signalingBrain areasWeight controlObesityGliosisEnergy homeostasisWeight gainInflammation
2003
Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice
Horvath TL, Diano S, Miyamoto S, Barry S, Gatti S, Alberati D, Livak F, Lombardi A, Moreno M, Goglia F, Mor G, Hamilton J, Kachinskas D, Horwitz B, Warden CH. Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice. International Journal Of Obesity 2003, 27: 433-442. PMID: 12664076, DOI: 10.1038/sj.ijo.0802257.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBasal MetabolismBlotting, NorthernBlotting, WesternBody TemperatureCarrier ProteinsCholesterol, LDLEnergy IntakeGene Expression RegulationHeart RateInflammationIon ChannelsMaleMembrane Transport ProteinsMiceMice, Inbred C57BLMice, TransgenicMitochondriaMitochondrial ProteinsObesityProteinsUncoupling Protein 2Uncoupling Protein 3ConceptsTransgenic miceFat massLow-density lipoprotein cholesterol levelsHeterozygous miceAgouti obese miceHypothalamic neuropeptide levelsSpontaneous physical activityLipoprotein cholesterol levelsNontransgenic littermate controlsFat pad weightEndotoxin-induced feverWild-type littermatesHuman UCP2Significant differencesMechanism of actionLDL cholesterolControl miceFemale transgenicsNontransgenic littermatesObese miceEndotoxin injectionCholesterol levelsPad weightNeuropeptide levelsFood intake