2022
A 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
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 ResearchConceptsAgRP 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 utilizationDefective autophagy in Sf1 neurons perturbs the metabolic response to fasting and causes mitochondrial dysfunction
Coupé B, Leloup C, Asiedu K, Maillard J, Pénicaud L, Horvath TL, Bouret SG. Defective autophagy in Sf1 neurons perturbs the metabolic response to fasting and causes mitochondrial dysfunction. Molecular Metabolism 2021, 47: 101186. PMID: 33571700, PMCID: PMC7907893, DOI: 10.1016/j.molmet.2021.101186.Peer-Reviewed Original ResearchConceptsLoss of Atg7Energy homeostasisCellular homeostasisGene Atg7Defective autophagyMitochondria morphologyPhysiological processesCellular responsesCellular componentsMetabolic responseMitochondrial dysfunctionAutophagyAtg7SF1 neuronsHomeostasisMutant miceNeurons displayLoxP/Energy expenditure regulationImportant roleVMH neuronsVentromedial nucleusLeptin sensitivityStarvationCentral response
2018
From 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 pathwaysBeigingObesityHypothalamusVMHPathway
2017
Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1
Rathjen T, Yan X, Kononenko NL, Ku MC, Song K, Ferrarese L, Tarallo V, Puchkov D, Kochlamazashvili G, Brachs S, Varela L, Szigeti-Buck K, Yi CX, Schriever SC, Tattikota SG, Carlo AS, Moroni M, Siemens J, Heuser A, van der Weyden L, Birkenfeld AL, Niendorf T, Poulet JFA, Horvath TL, Tschöp MH, Heinig M, Trajkovski M, Haucke V, Poy MN. Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1. Nature Neuroscience 2017, 20: 1096-1103. PMID: 28628102, PMCID: PMC5533218, DOI: 10.1038/nn.4590.Peer-Reviewed Original Research
2015
Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding
Waterson MJ, Horvath TL. Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding. Cell Metabolism 2015, 22: 962-970. PMID: 26603190, DOI: 10.1016/j.cmet.2015.09.026.Peer-Reviewed Original ResearchDevelopmental programming of hypothalamic neuroendocrine systems
Ralevski A, Horvath TL. Developmental programming of hypothalamic neuroendocrine systems. Frontiers In Neuroendocrinology 2015, 39: 52-58. PMID: 26391503, DOI: 10.1016/j.yfrne.2015.09.002.Peer-Reviewed Original ResearchConceptsHypothalamic neuroendocrine systemsDevelopmental programmingNeuroendocrine systemMetabolic fateMetabolic syndromeHypothalamic circuitsPerinatal environmentPossible cognitive impairmentMetabolic programmingCognitive impairmentMetabolic influencesEnergy homeostasisCritical periodNeural systemsSyndromeThe role of the hypothalamus in the maintenance of energy balance and peripheral glucose control
Varela L, Horvath T. The role of the hypothalamus in the maintenance of energy balance and peripheral glucose control. 2015, 529-537. DOI: 10.1002/9781118387658.ch36.Peer-Reviewed Original ResearchEnergy homeostasisPrevalence of obesityAnorectic hormonesAgRP neuronsHypothalamic POMCObese patientsGlucose controlGlucose homeostasisBody weightInsulin actionHormonal actionLeptinMajor targetInsulinHormoneBrainHomeostasisLatest findingsEnergy balanceSteady riseObesityPatientsHypothalamusPathwayPrevalence
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 receptorsMiceMolecular and cellular regulation of hypothalamic melanocortin neurons controlling food intake and energy metabolism
Koch M, Horvath TL. Molecular and cellular regulation of hypothalamic melanocortin neurons controlling food intake and energy metabolism. Molecular Psychiatry 2014, 19: 752-761. PMID: 24732669, DOI: 10.1038/mp.2014.30.Peer-Reviewed Original ResearchConceptsHypothalamic melanocortin neuronsEnergy metabolismFood intakePotential functional interactionsMelanocortin neuronsCellular regulationCellular processesFunctional interactionNeuronal circuit activityCellular mechanismsPhysiological behaviorEnergy homeostasisMetabolic eventsRegulationHypothalamic neuronsMetabolic healthObese individualsChronic overloadGlial cellsPhysical activityMetabolic disordersMelanocortin systemNeuronal circuitryCentral connectionsPsychiatric diseases
2012
Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis
Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Reports 2012, 13: 1079-1086. PMID: 23146889, PMCID: PMC3512417, DOI: 10.1038/embor.2012.174.Peer-Reviewed Original ResearchConceptsGlucose homeostasisEnergy homeostasisPrevalence of obesityWhole-body energy homeostasisBody energy homeostasisAnorectic hormonesAgRP neuronsObese patientsProtein (AgRP) neuronsCentral effectsHypothalamic proopiomelanocortinBody weightInsulin actionLeptinHormonal actionMajor targetInsulin pathwayHomeostasisInsulinNeuronsHormoneBrainLatest findingsEnergy balanceSteady risemTOR Signaling Fades POMC Neurons during Aging
Kim JG, Horvath TL. mTOR Signaling Fades POMC Neurons during Aging. Neuron 2012, 75: 356-357. PMID: 22884318, DOI: 10.1016/j.neuron.2012.07.017.Peer-Reviewed Original ResearchSirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism
Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath TL, Sinclair DA, Pfluger PT, Tschöp MH. Sirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism. Physiological Reviews 2012, 92: 1479-1514. PMID: 22811431, PMCID: PMC3746174, DOI: 10.1152/physrev.00022.2011.Peer-Reviewed Original ResearchConceptsSirtuin 1Sirtuin 3Nonalcoholic fatty liver diseaseMammalian sirtuin 1Multiple metabolic benefitsFatty liver diseaseDiet-induced obesityType 2 diabetesActivation of sirtuinsLiver diseaseCellular energy storesMetabolic benefitsMetabolic disordersPharmacological meansEnergy homeostasisPhysiological modulatorDependent deacetylasesMetabolic processesSirtuinsCellular energy homeostasisEnergy storesCellular sensorsEnergy statusAnabolic processesCatabolic processNeuroendocrine Regulation of Energy Metabolism
Dietrich M, Horvath T. Neuroendocrine Regulation of Energy Metabolism. Endocrinology And Metabolism 2012, 27: 268-273. DOI: 10.3803/enm.2012.27.4.268.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPeripheral metabolic signalsEnergy expenditureBrain homeostatic systemsMechanism of actionBrain involvementChronic regulationPharmacological techniquesNeuronal controlNeuroendocrine regulationNeuronal mechanismsEnergy homeostasisComplex feeding behaviorHomeostatic systemMetabolic signalsReview articleFeeding behaviorInvolvementCurrent understandingBrain
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 gainInflammationGhrelin Enhances Olfactory Sensitivity and Exploratory Sniffing in Rodents and Humans
Tong J, Mannea E, Aimé P, Pfluger PT, Yi CX, Castaneda TR, Davis HW, Ren X, Pixley S, Benoit S, Julliard K, Woods SC, Horvath TL, Sleeman MM, D'Alessio D, Obici S, Frank R, Tschöp MH. Ghrelin Enhances Olfactory Sensitivity and Exploratory Sniffing in Rodents and Humans. Journal Of Neuroscience 2011, 31: 5841-5846. PMID: 21490225, PMCID: PMC3089941, DOI: 10.1523/jneurosci.5680-10.2011.Peer-Reviewed Original ResearchConceptsExploratory sniffingAppetite-stimulating hormone ghrelinOlfactory sensitivityOverall functionGhrelin infusionIntracerebroventricular ghrelinGhrelin receptorHormone ghrelinSaline infusionOlfactory functionNeuroendocrine circuitsGhrelinUnderlying neural mechanismsEnergy homeostasisOdor detectionOlfactory processingOlfactory circuitFood seekingNeural mechanismsSniff magnitudeInfusionNovel roleOlfactory detectionSniffingSpecific effectsEffects 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
2009
Divergent Regulation of Energy Expenditure and Hepatic Glucose Production by Insulin Receptor in Agouti-Related Protein and POMC Neurons
Lin HV, Plum L, Ono H, Gutiérrez-Juárez R, Shanabrough M, Borok E, Horvath TL, Rossetti L, Accili D. Divergent Regulation of Energy Expenditure and Hepatic Glucose Production by Insulin Receptor in Agouti-Related Protein and POMC Neurons. Diabetes 2009, 59: 337-346. PMID: 19933998, PMCID: PMC2809966, DOI: 10.2337/db09-1303.Peer-Reviewed Original ResearchConceptsHepatic glucose productionAgRP neuronsPOMC neuronsInsulin receptorEnergy expenditureInsulin actionGlucose productionInhibitory synaptic contactsSulfonylurea receptor 1 (SUR1) subunitsCentral nervous systemL1 miceProopiomelanocortin neuronsHypothalamic insulinDivergent regulationInsulin resistanceSynaptic contactsInsulin suppressionGlucose metabolismHypothalamic deficiencyNervous systemLocomotor activityDecreased expressionEnergy homeostasisINSRNeuronsGABA Keeps Up an Appetite for Life
Dietrich MO, Horvath TL. GABA Keeps Up an Appetite for Life. Cell 2009, 137: 1177-1179. PMID: 19563747, DOI: 10.1016/j.cell.2009.06.002.Peer-Reviewed Original Research
2008
Fuel utilization by hypothalamic neurons: roles for ROS
Horvath TL, Andrews ZB, Diano S. Fuel utilization by hypothalamic neurons: roles for ROS. Trends In Endocrinology And Metabolism 2008, 20: 78-87. PMID: 19084428, DOI: 10.1016/j.tem.2008.10.003.Peer-Reviewed Original ResearchConceptsEnergy homeostasisFree radical productionAnorexigenic neuronsNeuronal doctrineArcuate nucleusHypothalamic neuronsHypothalamic outputMelanocortin systemEffect of glucoseNeuronal functionFree radical formationSpecific neuronsAcid levelsNeuronsAmino acid levelsNeurobiological aspectsRadical productionEvidence pointsFatty acidsFuel sensingIntracellular substratesHomeostasisNutritional signalsGlucoseHypothalamus