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 functionsDeficiencyKisspeptin signaling in astrocytes modulates the reproductive axis
Torres E, Pellegrino G, Granados-Rodríguez M, Fuentes-Fayos A, Velasco I, Coutteau-Robles A, Legrand A, Shanabrough M, Perdices-Lopez C, Leon S, Yeo S, Manchishi S, Sánchez-Tapia M, Navarro V, Pineda R, Roa J, Naftolin F, Argente J, Luque R, Chowen J, Horvath T, Prevot V, Sharif A, Colledge W, Tena-Sempere M, Romero-Ruiz A. Kisspeptin signaling in astrocytes modulates the reproductive axis. Journal Of Clinical Investigation 2024, 134: e172908. PMID: 38861336, PMCID: PMC11291270, DOI: 10.1172/jci172908.Peer-Reviewed Original ResearchResponse to metabolic stressProtein-protein interactionsMetabolic stressOntology analysisReproductive axisKisspeptin signalingGene expressionKisspeptin actionHypothalamic GnRH neuronsProteomic profilingFemale pubertal onsetReproductive modulesExpression of KISS1RLH secretory profilesSignaling-pathwayCellular co-expressionConditional ablationResponse to kisspeptinLH responses to kisspeptinNon-neuronal pathwaysAstrocytes in vivoHigh-fat dietGFAP-positive cellsPathwayReproductive controlCancer-associated hypercalcemia signals through the hindbrain to cause anorexia
Grinman D, Dann P, Shanabrough M, Horvath T, Wysolmerski J. Cancer-associated hypercalcemia signals through the hindbrain to cause anorexia. Journal Of Bone Oncology 2024, 45: 100535. DOI: 10.1016/j.jbo.2024.100535.Peer-Reviewed Original ResearchmicroRNA-33 controls hunger signaling in hypothalamic AgRP neurons
Price N, Fernández-Tussy P, Varela L, Cardelo M, Shanabrough M, Aryal B, de Cabo R, Suárez Y, Horvath T, Fernández-Hernando C. microRNA-33 controls hunger signaling in hypothalamic AgRP neurons. Nature Communications 2024, 15: 2131. PMID: 38459068, PMCID: PMC10923783, DOI: 10.1038/s41467-024-46427-0.Peer-Reviewed Original ResearchConceptsAgRP neuronsFeeding behaviorFatty acid metabolismNon-coding RNAsMitochondrial biogenesisRegulatory pathwaysTarget genesHypothalamic AgRP neuronsExcessive nutrient intakeCentral regulatorBioenergetic processesAcid metabolismActivation of AgRP neuronsModulate feeding behaviorCentral regulation of feeding behaviorRegulation of feeding behaviorMiR-33Hunger signalsMicroRNA-33Metabolic diseasesAlternative therapeutic approachLoss of miR-33Mouse modelMetabolic dysfunctionRegulation
2022
TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons
Xie D, Stutz B, Li F, Chen F, Lv H, Sestan-Pesa M, Catarino J, Gu J, Zhao H, Stoddard CE, Carmichael GG, Shanabrough M, Taylor HS, Liu ZW, Gao XB, Horvath TL, Huang Y. TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons. Journal Of Clinical Investigation 2022, 132: e162365. PMID: 36189793, PMCID: PMC9525119, DOI: 10.1172/jci162365.Peer-Reviewed Original ResearchConceptsAgRP neuronsNeuropeptide YExpression of AgRPControl of feedingHypothalamic agoutiAnxiolytic effectsNeurotransmitter GABAMouse modelLeptin signalingStress-like behaviorsGenetic ablationNeuronsAgRPCritical central regulatorsEnergy expenditureGABAEnergy metabolismAppetiteFeedingCentral regulatorMetabolismCentral controlHuman cellsTET3ObesityLINE-1 activation in the cerebellum drives ataxia
Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu ZW, Kristant A, Zhang Y, Sulkowski P, Glazer PM, Kaczmarek LK, Horvath TL, Iwasaki A. LINE-1 activation in the cerebellum drives ataxia. Neuron 2022, 110: 3278-3287.e8. PMID: 36070749, PMCID: PMC9588660, DOI: 10.1016/j.neuron.2022.08.011.Peer-Reviewed Original ResearchConceptsLINE-1 activationL1 activationAtaxia telangiectasia patientsNuclear element-1Transposable elementsEpigenetic silencersHuman genomeL1 promoterMolecular regulatorsDNA damagePurkinje cell dysfunctionElement 1First direct evidenceTelangiectasia patientsDirect targetingCerebellar expressionNeurodegenerative diseasesDisease etiologyCalcium homeostasisA hypothalamic pathway for Augmentor α–controlled body weight regulation
Ahmed M, Kaur N, Cheng Q, Shanabrough M, Tretiakov EO, Harkany T, Horvath TL, Schlessinger J. A hypothalamic pathway for Augmentor α–controlled body weight regulation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2200476119. PMID: 35412887, PMCID: PMC9169862, DOI: 10.1073/pnas.2200476119.Peer-Reviewed Original ResearchConceptsParaventricular nucleusBody weightDiet-induced obesityBody weight regulationDiscrete neuronal populationsMelanocortin receptor 4Whole-body energy homeostasisPhysiological rolePeptide neuronsHypothalamic pathwaysReceptor 4Neuronal pathwaysPhysical activityLittermate controlsWeight regulationNeuronal populationsMetabolic diseasesTherapeutic opportunitiesMutant miceEnergy homeostasisMiceALKCancerHuman cancersALK mutants
2021
Author Correction: AgRP neurons control compulsive exercise and survival in an activity-based anorexia model
Miletta MC, Iyilikci O, Shanabrough M, Šestan-Peša M, Cammisa A, Zeiss CJ, Dietrich MO, Horvath TL. Author Correction: AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nature Metabolism 2021, 3: 288-288. PMID: 33495625, DOI: 10.1038/s42255-021-00351-5.Peer-Reviewed Original Research
2020
AgRP neurons control compulsive exercise and survival in an activity-based anorexia model
Miletta MC, Iyilikci O, Shanabrough M, Šestan-Peša M, Cammisa A, Zeiss CJ, Dietrich MO, Horvath TL. AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nature Metabolism 2020, 2: 1204-1211. PMID: 33106687, DOI: 10.1038/s42255-020-00300-8.Peer-Reviewed Original ResearchConceptsAgRP neuronsActivity-based anorexia modelAgRP neuronal activityVivo fiber photometryFood-restricted miceFood-restricted animalsCompulsive exerciseAnorexia modelHypothalamic agoutiNeuropeptide YExercise volumeFood intakeMouse modelNeuronal activityFiber photometryDaily activationNeuronal circuitsPsychiatric conditionsAnorexia nervosaChemogenetic toolsNeuronsLong-term behavioral impactElevated fat contentVoluntary cessationFat contentNesfatin-1 decreases the motivational and rewarding value of food
Dore R, Krotenko R, Reising JP, Murru L, Sundaram SM, Di Spiezio A, Müller-Fielitz H, Schwaninger M, Jöhren O, Mittag J, Passafaro M, Shanabrough M, Horvath TL, Schulz C, Lehnert H. Nesfatin-1 decreases the motivational and rewarding value of food. Neuropsychopharmacology 2020, 45: 1645-1655. PMID: 32353862, PMCID: PMC7419560, DOI: 10.1038/s41386-020-0682-3.Peer-Reviewed Original ResearchConceptsNUCB2/nesfatinNesfatin-1Nucleobindin-2Food intakeNesfatin-1 actionDopaminergic neuron activityFasting-induced increaseReward-related brain areasOutward potassium currentHedonic pathwaysHedonic feedingGABA neuronsLeptin resistanceBrain areasPotassium currentNeuron activityFood rewardEnergy intakeReward circuitryElectrophysiological recordingsNesfatinCentral administrationEnhanced sensitizationIntakeHomeostatic mechanisms
2017
Ghrelin is Related to Personality Differences in Reward Sensitivity and Impulsivity
Ralevski E, Shanabrough M, Newcomb J, Gandelman E, Hayden R, Horvath TL, Petrakis I. Ghrelin is Related to Personality Differences in Reward Sensitivity and Impulsivity. Alcohol And Alcoholism 2017, 53: 52-56. PMID: 29136100, DOI: 10.1093/alcalc/agx082.Peer-Reviewed Original ResearchConceptsAspects of impulsivityTraits of impulsivityHealthy social drinkersSocial drinkersReward sensitivityImpulsivity traitsPersonality measuresPersonality differencesImpulsivityDrugs of abusePersonality characteristicsSubjective effectsDirect relationshipHigh levelsDrinkersFeeding-related peptidesPunishmentFirst studyIndividualsTraitsSecondary analysisParticipantsAbuseRelationshipOriginal studyGhrelin is Supressed by Intravenous Alcohol and is Related to Stimulant and Sedative Effects of Alcohol
Ralevski E, Horvath TL, Shanabrough M, Hayden R, Newcomb J, Petrakis I. Ghrelin is Supressed by Intravenous Alcohol and is Related to Stimulant and Sedative Effects of Alcohol. Alcohol And Alcoholism 2017, 52: 431-438. PMID: 28481974, DOI: 10.1093/alcalc/agx022.Peer-Reviewed Original ResearchConceptsGhrelin levelsDoses of alcoholHealthy social drinkersSubjective effectsTG levelsAlcohol infusionSedative effectsLow doseHigh doseOral alcohol administrationIntravenous alcohol infusionFeeding-related peptidesSocial drinkersAlcohol administrationIntravenous alcoholOral alcoholGhrelinPercent changeInfusionRewarding propertiesBehavioral effectsAlcohol effectsDoseTime pointsSignificant predictorsEndothelial 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
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
2015
Bcl-xL Is Necessary for Neurite Outgrowth in Hippocampal Neurons
Park HA, Licznerski P, Alavian KN, Shanabrough M, Jonas EA. Bcl-xL Is Necessary for Neurite Outgrowth in Hippocampal Neurons. Antioxidants & Redox Signaling 2015, 22: 93-108. PMID: 24787232, PMCID: PMC4281845, DOI: 10.1089/ars.2013.5570.Peer-Reviewed Original ResearchConceptsDeath receptor 6Hippocampal neuronsNeurite outgrowthExacerbation of hypoxiaBcl-xLNeuronal outgrowthNeuronal process outgrowthNeuronal injuryNeurodegenerative stimuliVivo ischemiaHypoxic injuryNeuronal survivalBrain injuryImpairs neurite outgrowthHypoxic controlsSynapse numberAxonal pruningNeurite damageB cellsReceptor 6Synaptic plasticityDR6 expressionSynapse formationEarly increaseNeurons
2013
Antibodies to cannabinoid type 1 receptor co‐react with stomatin‐like protein 2 in mouse brain mitochondria
Morozov YM, Dominguez MH, Varela L, Shanabrough M, Koch M, Horvath TL, Rakic P. Antibodies to cannabinoid type 1 receptor co‐react with stomatin‐like protein 2 in mouse brain mitochondria. European Journal Of Neuroscience 2013, 38: 2341-2348. PMID: 23617247, PMCID: PMC3902808, DOI: 10.1111/ejn.12237.Peer-Reviewed Original ResearchConceptsStomatin-like protein 2Type 1 receptorPresence of CB1Protein 2Anti-CB1 antibodySynthetic cannabinoid WINMouse brain mitochondriaCerebral cortexEndocannabinoid signalingBrain cellsCannabinoid WINNeuronal mitochondriaBrain mitochondriaAntibodiesMitochondrial functionCB1Polyclonal antibodiesCortexMitochondrial preparationsSerumReceptors
2011
Erratum: Corrigendum: Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity
Diano S, Liu Z, Jeong J, Dietrich M, Ruan H, Kim E, Suyama S, Kelly K, Gyengesi E, Arbiser J, Belsham D, Sarruf D, Schwartz M, Bennett A, Shanabrough M, Mobbs C, Yang X, Gao X, Horvath T. Erratum: Corrigendum: Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nature Medicine 2011, 17: 1320-1320. DOI: 10.1038/nm1011-1320a.Peer-Reviewed Original ResearchPeroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity
Diano S, Liu ZW, Jeong JK, Dietrich MO, Ruan HB, Kim E, Suyama S, Kelly K, Gyengesi E, Arbiser JL, Belsham DD, Sarruf DA, Schwartz MW, Bennett AM, Shanabrough M, Mobbs CV, Yang X, Gao XB, Horvath TL. Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nature Medicine 2011, 17: 1121-1127. PMID: 21873987, PMCID: PMC3388795, DOI: 10.1038/nm.2421.Peer-Reviewed Original ResearchEffects 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 structuresMaternal Ghrelin Deficiency Compromises Reproduction in Female Progeny through Altered Uterine Developmental Programming
Martin JR, Lieber SB, McGrath J, Shanabrough M, Horvath TL, Taylor HS. Maternal Ghrelin Deficiency Compromises Reproduction in Female Progeny through Altered Uterine Developmental Programming. Endocrinology 2011, 152: 2060-2066. PMID: 21325042, PMCID: PMC3075930, DOI: 10.1210/en.2010-1485.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEmbryo ImplantationFemaleFertilityGene Expression Regulation, DevelopmentalGhrelinHeterozygoteHomeobox A10 ProteinsHomeodomain ProteinsImmunohistochemistryLitter SizeMaleMiceMice, KnockoutProliferating Cell Nuclear AntigenReproductionReverse Transcriptase Polymerase Chain ReactionTranscription FactorsUterusWnt ProteinsConceptsGhrelin deficiencyDevelopmental programmingAbnormal endometrial functionFemale wild-type miceUterus of miceLevels of ghrelinRegulation of appetiteWild-type miceReproductive tract developmentWild-type offspringSubsequent subfertilityEndometrial proliferationUnexposed miceEndometrial functionUtero exposureUterine expressionEmbryo implantationOvarian folliclesCorpora luteaGhrelinReproductive tractTract developmentMiceSignificant alterationsSubfertility