2024
Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation
Mohr S, Dai Pra R, Platt M, Feketa V, Shanabrough M, Varela L, Kristant A, Cao H, Merriman D, Horvath T, Bagriantsev S, Gracheva E. Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation. Nature Communications 2024, 15: 5803. PMID: 38987241, PMCID: PMC11236985, DOI: 10.1038/s41467-024-49996-2.Peer-Reviewed Original ResearchConceptsHypothalamic feeding centersHormone deficiencyHypothalamic arcuate nucleus neuronsArcuate nucleus neuronsThyroid hormone deficiencyFeeding centerEffects of ghrelinAnorexigenic effectNucleus neuronsPhysiological anorexiaThyroid hormonesNormal physiological functionsGround squirrelsInterbout arousalAnorexiaThirteen-lined ground squirrelsProlonged periodReduced sensitivityPhysiological functionsDeficiency
2022
AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids
Endle H, Horta G, Stutz B, Muthuraman M, Tegeder I, Schreiber Y, Snodgrass IF, Gurke R, Liu ZW, Sestan-Pesa M, Radyushkin K, Streu N, Fan W, Baumgart J, Li Y, Kloss F, Groppa S, Opel N, Dannlowski U, Grabe HJ, Zipp F, Rácz B, Horvath TL, Nitsch R, Vogt J. AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids. Nature Metabolism 2022, 4: 683-692. PMID: 35760867, PMCID: PMC9940119, DOI: 10.1038/s42255-022-00589-7.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsDiabetes Mellitus, Type 2Feeding BehaviorHumansHyperphagiaLysophospholipidsMiceNeuronsSynapsesConceptsFasting-induced hyperphagiaCortical excitabilityAgRP neuronsLysophosphatidic acidPeripheral metabolismHigher body mass indexFasting-induced elevationHypothalamic AgRP neuronsEffects of LPABody mass indexHigher cortical excitabilityBrain lipid levelsCentral nervous systemPrevalence of typeGlutamatergic transmissionHypothalamic agoutiMass indexOvernight fastingPeptide neuronsCortical synapsesLipid levelsFood intakeCerebrospinal fluidNervous systemPhospholipid levels
2021
Drp1 is required for AgRP neuronal activity and feeding
Jin S, Yoon NA, Liu ZW, Song JE, Horvath TL, Kim JD, Diano S. Drp1 is required for AgRP neuronal activity and feeding. ELife 2021, 10: e64351. PMID: 33689681, PMCID: PMC7946429, DOI: 10.7554/elife.64351.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsBody WeightDynaminsEnergy MetabolismFastingFeeding BehaviorFemaleMaleMiceNeuronsConceptsAgRP neuronal activityFatty acid oxidationAgRP neuronsNeuronal activityAgRP neuronal functionHypothalamic AgRP neuronsBody weight regulationMitochondrial fatty acid utilizationWhole-body energy homeostasisHypothalamic orexigenic agoutiFatty acid utilizationAcid oxidationFat massCKO miceNeuronal activationPeptide-1Body weightNeuronal functionOrexigenic agoutiEnergy homeostasisMitochondrial fissionSignificant decreaseEnergy expenditureNeuronsAcid utilization
2020
Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice
Tan Y, Hang F, Liu ZW, Stoiljkovic M, Wu M, Tu Y, Han W, Lee AM, Kelley C, Hajos M, Lu L, de Lecea L, de Araujo I, Picciotto M, Horvath TL, Gao XB. Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice. Journal Of Clinical Investigation 2020, 130: 4985-4998. PMID: 32516139, PMCID: PMC7456212, DOI: 10.1172/jci130889.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFeeding BehaviorHypothalamusMaleMiceMice, TransgenicNerve NetNeuronsObesityOrexinsStress, PsychologicalConceptsHcrt cellsObese miceDiet-induced obese miceObese male miceExcessive energy intakeNeuropeptide hypocretin/orexinHypocretin/orexinHcrt neuronsMale miceHcrt systemClinical studiesCommon causeSynaptic transmissionObese animalsEnergy intakeAcute stressCognitive functionSalient stimuliAlters responsesExact mechanismMiceHomeostatic regulationNeuronal networksBehavioral changesNeurons
2019
Parallel Paths in PVH Control of Feeding
Varela L, Horvath TL. Parallel Paths in PVH Control of Feeding. Neuron 2019, 102: 514-516. PMID: 31071283, DOI: 10.1016/j.neuron.2019.04.026.Peer-Reviewed Original Research
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 levelsNeuroinflammationSIRT1DietDeficiency
2016
Feeding Behavior: Hypocretin/Orexin Neurons Act between Food Seeking and Eating
Gao XB, Horvath TL. Feeding Behavior: Hypocretin/Orexin Neurons Act between Food Seeking and Eating. Current Biology 2016, 26: r845-r847. PMID: 27676302, DOI: 10.1016/j.cub.2016.07.069.Peer-Reviewed Original ResearchMetabolism and Mental Illness
Sestan-Pesa M, Horvath TL. Metabolism and Mental Illness. Trends In Molecular Medicine 2016, 22: 174-183. PMID: 26776095, DOI: 10.1016/j.molmed.2015.12.003.Peer-Reviewed Original ResearchConceptsCentral nervous systemMental illnessBasic metabolic principlesHigher brain functionsCerebral cortexNovel therapiesNervous systemBrain functionSystemic controlPathological conditionsIllnessAppetiteCrucial regulatorFuture research strategiesOverwhelming evidenceMetabolic principlesFeeding behaviorMetabolismHypothalamusTherapyCortexBrain
2015
Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding
Dietrich MO, Zimmer MR, Bober J, Horvath TL. Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding. Cell 2015, 160: 1222-1232. PMID: 25748653, PMCID: PMC4484787, DOI: 10.1016/j.cell.2015.02.024.Peer-Reviewed Original ResearchConceptsHypothalamic AgRP neuronsAgRP neuronsNeuropeptidergic signalingReceptor signalingFunctional rolePotential therapeutic avenuesAgRP neuron activationStereotypic behaviorFeeding behaviorRepetitive behaviorsSignalingTherapeutic avenuesFood triggersAdult miceNervous systemDecreased anxietyNeuronsMinor effectActivationFood consumptionNeuron activationGoal-directed behaviorSensory informationFlexible goal-directed behaviorDisease
2014
A 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
2012
Reward Aspects of Gastrointestinal Hormones Mediated by Brain G Protein–Coupled Receptors
Koch M, Horvath TL. Reward Aspects of Gastrointestinal Hormones Mediated by Brain G Protein–Coupled Receptors. Biological Psychiatry 2012, 72: 340-342. PMID: 22872010, DOI: 10.1016/j.biopsych.2012.06.031.Peer-Reviewed Original Research
2010
Enhanced anorexigenic signaling in lean obesity resistant syndecan-3 null mice
Zheng Q, Zhu J, Shanabrough M, Borok E, Benoit SC, Horvath TL, Clegg DJ, Reizes O. Enhanced anorexigenic signaling in lean obesity resistant syndecan-3 null mice. Neuroscience 2010, 171: 1032-1040. PMID: 20923696, PMCID: PMC2991621, DOI: 10.1016/j.neuroscience.2010.09.060.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAlpha-MSHAnalysis of VarianceAnimalsBody WeightDose-Response Relationship, DrugEatingFeeding BehaviorFood DeprivationGene Expression RegulationMaleMiceMice, KnockoutNeuronsNeuropeptide YParaventricular Hypothalamic NucleusProto-Oncogene Proteins c-fosSignal TransductionSyndecan-3Time FactorsConceptsMelanocortin agonist melanotan IISyndecan-3 null miceParaventricular nucleusBody weightNull miceHypothalamic target neuronsNeuropeptide α-MSHRisk of diabetesC-Fos immunoreactivityHypothalamic paraventricular nucleusBody weight regulationWild-type miceTypes of cancerAnorexigenic αAgRP neuronsHormone neuronsHypothalamic circuitsNeuropeptide YAnorexigenic signalingNeuropeptide responsesCardiovascular diseaseFood intakeTarget neuronsMelanotan IIType mice
2009
Feeding signals and brain circuitry
Dietrich MO, Horvath TL. Feeding signals and brain circuitry. European Journal Of Neuroscience 2009, 30: 1688-1696. PMID: 19878280, DOI: 10.1111/j.1460-9568.2009.06963.x.Peer-Reviewed Original ResearchReduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice
Blum ID, Patterson Z, Khazall R, Lamont EW, Sleeman MW, Horvath TL, Abizaid A. Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice. Neuroscience 2009, 164: 351-359. PMID: 19666088, PMCID: PMC2996828, DOI: 10.1016/j.neuroscience.2009.08.009.Peer-Reviewed Original ResearchConceptsAnticipatory locomotor activityGHSR KO miceLocomotor activityKO miceGhrelin receptor deficient miceReceptor-deficient miceFeeding scheduleFos expression patternsWild-type littermatesRestricted feeding scheduleGhrelin receptor geneGhrelin injectionOrexigenic hormoneFos immunoreactivityHypothalamic nucleiDeficient miceLocomotor responseGhrelinH dailyMiceReceptor geneMealH patternTargeted mutationsBehavioral measures
2008
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL, Diano S. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature 2008, 454: 846-851. PMID: 18668043, PMCID: PMC4101536, DOI: 10.1038/nature07181.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsCarnitine O-PalmitoyltransferaseFatty AcidsFeeding BehaviorGene Expression RegulationGhrelinHypothalamusIon ChannelsMembrane Potential, MitochondrialMiceMitochondriaMitochondrial ProteinsNeuronsNeuropeptide YPhosphorylationReactive Oxygen SpeciesSynapsesUncoupling Protein 2ConceptsNPY/AgRP neuronsAgRP neuronsNeuronal activityCo-express neuropeptide YGut-derived hormone ghrelinAgRP neuronal activityArcuate nucleus neuronsFatty acid oxidation pathwayHypothalamic mitochondrial respirationG protein-coupled receptorsGhrelin actionNeuropeptide YNucleus neuronsHormone ghrelinFood intakeGhrelinFree radicalsSynaptic plasticityNeuronal functionIntracellular mechanismsNeuronsMitochondrial mechanismsProtein 2Mitochondrial proliferationRobust changes
2007
Neuronal control of energy homeostasis
Gao Q, Horvath TL. Neuronal control of energy homeostasis. FEBS Letters 2007, 582: 132-141. PMID: 18061579, PMCID: PMC4113225, DOI: 10.1016/j.febslet.2007.11.063.Peer-Reviewed Original ResearchConceptsEnergy homeostasisNeuronal controlMolecular genetic toolsPeripheral metabolic hormonesHypothalamic neuronal circuitsLong-term energy balanceBody energy homeostasisGenetic toolsHomeostatic machineryMetabolic hormonesNeuronal activityNeuronal circuitryBody weightEnergy intakeNeuronal circuitsCellular mechanismsHomeostasisBehavioral techniquesLife spanKey mechanismMachineryIntakeHormoneNeurobiology of Feeding and Energy Expenditure
Gao Q, Horvath TL. Neurobiology of Feeding and Energy Expenditure. Annual Review Of Neuroscience 2007, 30: 367-398. PMID: 17506645, DOI: 10.1146/annurev.neuro.30.051606.094324.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAppetite RegulationEnergy MetabolismFeeding BehaviorHormonesHumansHypothalamusLeptinMelanocortinsMotivationNeural PathwaysConceptsEnergy expenditureNeurobiology of feedingPeripheral metabolic signalsBrain homeostatic systemsMechanism of actionBrain involvementChronic regulationPharmacological techniquesNeuronal controlNeuronal mechanismsEnergy homeostasisComplex feeding behaviorHomeostatic systemMetabolic signalsFeeding behaviorInvolvementCurrent understandingBrainA Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2
Coppola A, Liu ZW, Andrews ZB, Paradis E, Roy MC, Friedman JM, Ricquier D, Richard D, Horvath TL, Gao XB, Diano S. A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2. Cell Metabolism 2007, 5: 21-33. PMID: 17189204, PMCID: PMC1783766, DOI: 10.1016/j.cmet.2006.12.002.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusEatingFastingFeeding BehaviorGreen Fluorescent ProteinsGuanosine DiphosphateHypothalamusIntercellular Signaling Peptides and ProteinsIodide PeroxidaseIon ChannelsMiceMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial ProteinsNeurogliaNeuronsNeuropeptide YProto-Oncogene Proteins c-fosThermogenesisTriiodothyronineUncoupling Protein 2ConceptsUncoupling protein 2Mitochondrial uncoupling protein 2Thyroid hormone productionProtein activityType 2 deiodinaseMitochondrial proliferationNeuropeptide YArcuate nucleusPhysiological roleMitochondrial uncouplingUCP2 activationProtein 2Hormone productionNPY/AgRP neuronsPhysiological significanceActive thyroid hormoneHypothalamic arcuate nucleusHypothalamic neuronal networksGlial cellsRebound feedingAgRP neuronsOrexigenic neuronsDeiodinaseDII activityPeripheral tissues
2005
Cannabinoids, opioids and eating behavior: The molecular face of hedonism?
Cota D, Tschöp MH, Horvath TL, Levine AS. Cannabinoids, opioids and eating behavior: The molecular face of hedonism? Brain Research Reviews 2005, 51: 85-107. PMID: 16364446, DOI: 10.1016/j.brainresrev.2005.10.004.Peer-Reviewed Original ResearchConceptsOpioid receptor antagonistPrevalence of obesityAnti-obesity drugsAnti-obesity therapiesCentral nervous mechanismsAddictive componentOpioid systemReceptor antagonistEnergy balance controlFood intakeNervous mechanismsAddictive propertiesEnergy homeostasisHealth threatLife expectancyBody of dataRewarding valueAlarming increaseObesityBalance controlHomeostatic componentWestern countriesFunctional interactionHedonic aspectsOpioidsA 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, G-Protein-CoupledReceptors, GhrelinTime 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