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
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 levelsNeurograninHypothalamusIntakeDietLoss of Nucleobindin-2 Causes Insulin Resistance in Obesity without Impacting Satiety or Adiposity
Ravussin A, Youm YH, Sander J, Ryu S, Nguyen K, Varela L, Shulman GI, Sidorov S, Horvath TL, Schultze JL, Dixit VD. Loss of Nucleobindin-2 Causes Insulin Resistance in Obesity without Impacting Satiety or Adiposity. Cell Reports 2018, 24: 1085-1092.e6. PMID: 30067966, PMCID: PMC6223120, DOI: 10.1016/j.celrep.2018.06.112.Peer-Reviewed Original ResearchConceptsHigh-fat dietInsulin resistanceFood intakeMetabolic inflammationNucleobindin-2M2-like macrophage polarizationHigh-fat diet feedingWeight lossAdipose tissue macrophagesObesity-associated diseasesNesfatin-1Insulin sensitivityDiet feedingMacrophage polarizationNUCB2 proteinMyeloid cellsTissue macrophagesGlobal deletionClassical M1NUCB2NFκB-dependent mannerWeight gainSatietyIntakeAdiposity
2014
PPARγ 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 receptorsMice
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 gainInflammationEffects of chronic weight perturbation on energy homeostasis and brain structure in mice
Ravussin Y, Gutman R, Diano S, Shanabrough M, Borok E, Sarman B, Lehmann A, LeDuc CA, Rosenbaum M, Horvath TL, Leibel RL. Effects of chronic weight perturbation on energy homeostasis and brain structure in mice. AJP Regulatory Integrative And Comparative Physiology 2011, 300: r1352-r1362. PMID: 21411766, PMCID: PMC3119157, DOI: 10.1152/ajpregu.00429.2010.Peer-Reviewed Original ResearchConceptsDiet-induced obeseEnergy expenditureArcuate nucleus proopiomelanocortin neuronsWeight lossWeight-reduced individualsSustained weight lossReduced body weightObese human subjectsCentral nervous systemHuman subjectsSustained weight gainProopiomelanocortin neuronsBody massUpward resettingMale miceExcitatory synapsesBody fatMouse modelBody weightNervous systemSynaptic changesPersistent decreaseEnergy homeostasisWeight gainBrain structures
2010
Uncoupling 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
2009
Correlation between body weight changes and postoperative pain in rats treated with meloxicam or buprenorphine
Brennan MP, Sinusas AJ, Horvath TL, Collins JG, Harding MJ. Correlation between body weight changes and postoperative pain in rats treated with meloxicam or buprenorphine. Lab Animal 2009, 38: 87-93. PMID: 19229225, PMCID: PMC2805902, DOI: 10.1038/laban0309-87.Peer-Reviewed Original ResearchConceptsPostoperative painBody weightAdult male Lewis ratsWeight changeMajor surgical proceduresGeneral endotracheal anesthesiaMale Lewis ratsEfficacy of meloxicamRat body weightYoung adult ratsBody weight changesBody weight gainBuprenorphine analgesiaPostoperative changesLewis ratsEndotracheal anesthesiaSurgical proceduresPhysiologic effectsAdult ratsControl groupPainBuprenorphineRatsNormal levelsWeight gain
2008
Cross-talk between estrogen and leptin signaling in the hypothalamus
Gao Q, Horvath TL. Cross-talk between estrogen and leptin signaling in the hypothalamus. AJP Endocrinology And Metabolism 2008, 294: e817-e826. PMID: 18334610, DOI: 10.1152/ajpendo.00733.2007.Peer-Reviewed Original ResearchConceptsAdipocyte-secreted hormone leptinGonadal steroid hormone estrogenAction of leptinMajor risk factorNeuroendocrine reproductive axisEnergy expenditureHalf of adultsSteroid hormone estrogenEnhanced food intakeFunction of estrogenEstrogen deficiencyRisk factorsHormone leptinCardiovascular diseaseHormone estrogenFood intakeBody fatReproductive axisLeptinEstrogenRegulation of reproductionEnergy homeostasisWeight gainEstrogen facilitatesNeuroendocrine processes
2006
Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals
Gao Q, Mezei G, Nie Y, Rao Y, Choi CS, Bechmann I, Leranth C, Toran-Allerand D, Priest CA, Roberts JL, Gao XB, Mobbs C, Shulman GI, Diano S, Horvath TL. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nature Medicine 2006, 13: 89-94. PMID: 17195839, DOI: 10.1038/nm1525.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnorexiaArcuate Nucleus of HypothalamusBody WeightEstradiolEstrogen Receptor alphaExcitatory Postsynaptic PotentialsFemaleInjections, IntraventricularLeptinMaleMelanocortinsMiceMice, Inbred C57BLMice, KnockoutMice, ObeseMicroscopy, ElectronNeuronsObesityOvariectomyPro-OpiomelanocortinRatsRats, Sprague-DawleySignal TransductionSTAT3 Transcription FactorConceptsArcuate nucleusFood intakeLeptin receptor-deficient miceGonadal steroid estradiolRearrangement of synapsesReceptor-deficient miceBody weight regulationBody weight gainWild-type ratsPOMC neuronsLeptin effectsExcitatory inputsMetabolic hormonesLeptin receptorObese animalsSteroids estradiolWeight regulationBody weightSynaptic plasticityWeight gainRobust increaseInput organizationSTAT3 activationEnergy expenditureAdiposity
2005
A Novel Growth Hormone Secretagogue-1a Receptor Antagonist That Blocks Ghrelin-Induced Growth Hormone Secretion but Induces Increased Body Weight Gain
Halem HA, Taylor JE, Dong JZ, Shen Y, Datta R, Abizaid A, Diano S, Horvath TL, Culler MD. A Novel Growth Hormone Secretagogue-1a Receptor Antagonist That Blocks Ghrelin-Induced Growth Hormone Secretion but Induces Increased Body Weight Gain. Neuroendocrinology 2005, 81: 339-349. PMID: 16210868, DOI: 10.1159/000088796.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArea Under CurveBehavior, AnimalBinding, CompetitiveBody WeightBrainCell CountCHO CellsCricetinaeCricetulusDose-Response Relationship, DrugDrug InteractionsFeeding BehaviorGhrelinGrowth HormoneHumansImmunohistochemistryIodine IsotopesMaleOncogene Proteins v-fosPeptide HormonesRatsRats, Sprague-DawleyReceptors, GhrelinReceptors, G-Protein-CoupledTime FactorsConceptsDorsal medial hypothalamusGHS-1a receptorGrowth hormone secretionBIM-28163Fos-IRWeight gainGH secretionHormone secretionGrowth hormone secretagogue 1a receptorAntagonist of ghrelinMedial arcuate nucleusAction of ghrelinFos protein immunoreactivityAnti-obesity strategiesBody weight gainGhrelin activationConcomitant administrationGhrelin actionMedial hypothalamusArcuate nucleusReceptor antagonistGhrelin receptorFood intakeProtein immunoreactivityHuman ghrelin
2004
Novel analogs of ghrelin: physiological and clinical implications
Halem H, Taylor J, Dong J, Shen Y, Datta R, Abizaid A, Diano S, Horvath T, Zizzari P, Bluet-Pajot M, Epelbaum J, Culler M. Novel analogs of ghrelin: physiological and clinical implications. European Journal Of Endocrinology 2004, 151: s71-s75. PMID: 15339248, DOI: 10.1530/eje.0.151s071.Peer-Reviewed Original ResearchConceptsBIM-28163GH secretionGHS receptorWeight gainNeuronal activationGrowth hormone secretagogue receptorAntagonist of ghrelinAction of ghrelinNormal GH secretionRole of ghrelinStimulation of feedingActivity of ghrelinPotential therapeutic benefitAnalogues of ghrelinNative ghrelinEndogenous ghrelinGhrelin actionGH levelsHypothalamic GHHypothalamic sitesSecretagogue receptorGhrelin receptorFood intakeNormal ratsGhrelin analogs