2021
Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis
Gómez-Valadés AG, Pozo M, Varela L, Boudjadja MB, Ramírez S, Chivite I, Eyre E, Haddad-Tóvolli R, Obri A, Milà-Guasch M, Altirriba J, Schneeberger M, Imbernón M, Garcia-Rendueles AR, Gama-Perez P, Rojo-Ruiz J, Rácz B, Alonso MT, Gomis R, Zorzano A, D’Agostino G, Alvarez CV, Nogueiras R, Garcia-Roves PM, Horvath TL, Claret M. Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis. Cell Metabolism 2021, 33: 1820-1835.e9. PMID: 34343501, PMCID: PMC8432968, DOI: 10.1016/j.cmet.2021.07.008.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsGTP PhosphohydrolasesHomeostasisLipolysisMiceNeuronsPro-OpiomelanocortinConceptsProtein OPA1Mitochondrial CaMitochondrial cristae architectureAdipose tissue lipolysisKey metabolic sensorPOMC neuronsCellular metabolic adaptationTissue lipolysisCristae architectureMetabolic sensorNutrient availabilityWhite adipose tissue lipolysisAlpha-melanocyte stimulating hormoneGenetic inactivationNovel axisMitochondrial functionOPA1Metabolic adaptationMitochondrial cristaeDramatic alterationsMutant miceProopiomelanocortin neuronsLipolysis controlWAT lipolysisPharmacological blockadeAdiponectin preserves metabolic fitness during aging
Li N, Zhao S, Zhang Z, Zhu Y, Gliniak CM, Vishvanath L, An YA, Wang MY, Deng Y, Zhu Q, Shan B, Sherwood A, Onodera T, Oz OK, Gordillo R, Gupta RK, Liu M, Horvath TL, Dixit VD, Scherer PE. Adiponectin preserves metabolic fitness during aging. ELife 2021, 10: e65108. PMID: 33904399, PMCID: PMC8099426, DOI: 10.7554/elife.65108.Peer-Reviewed Original ResearchConceptsAdiponectin null miceSystemic insulin sensitivityInsulin sensitivityNull miceAge-related glucoseRole of adiponectinLipid metabolism disordersHigh-fat dietTransgenic mouse modelAdiponectin levelsTissue inflammationMetabolism disordersClinical studiesMouse modelAdiponectinMice displayMetabolic fitnessOverexpression modelPositive associationMiceMedian lifespanHealthspanDirect effectEssential regulatorAging processDefective 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
2020
Metabolic Lateralization in the Hypothalamus of Male Rats Related to Reproductive and Satiety States
Kiss DS, Toth I, Jocsak G, Bartha T, Frenyo LV, Barany Z, Horvath TL, Zsarnovszky A. Metabolic Lateralization in the Hypothalamus of Male Rats Related to Reproductive and Satiety States. Reproductive Sciences 2020, 27: 1197-1205. PMID: 32046448, PMCID: PMC7181557, DOI: 10.1007/s43032-019-00131-3.Peer-Reviewed Original ResearchConceptsSatiety stateMale ratsFood intakeImpact of gonadectomyRight hemisphereSleep-wake behaviorHypothalamic functionMale rodentsMetabolic asymmetryScheduled feedingFunctional lateralizationHypothalamusEx vivoRegulatory centersRatsMetabolic differencesHomeostatic processesFunctional asymmetryIntakeLateralizationRecent findingsPresent studyReproductive controlGonadectomySatiety
2018
Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity
Timper K, Paeger L, Sánchez-Lasheras C, Varela L, Jais A, Nolte H, Vogt MC, Hausen AC, Heilinger C, Evers N, Pospisilik JA, Penninger JM, Taylor EB, Horvath TL, Kloppenburg P, Brüning JC. Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity. Cell Reports 2018, 25: 383-397.e10. PMID: 30304679, PMCID: PMC6349418, DOI: 10.1016/j.celrep.2018.09.034.Peer-Reviewed Original ResearchConceptsPOMC neuronsApoptosis-inducing factorImproved glucose metabolismFatty acid utilizationDecrease firingPomc-CreFatty acid metabolismHFD feedingReactive oxygen species formationSystemic glucoseHypothalamic proopiomelanocortinLean miceMitochondrial respirationObese miceObese conditionsInsulin sensitivityGlucose homeostasisGlucose metabolismMild impairmentOxygen species formationFiring propertiesNeuronsOxidative phosphorylationMicePartial impairmentViral Vectors for Studying Brain Mechanisms that Control Energy Homeostasis
Mancini G, Horvath TL. Viral Vectors for Studying Brain Mechanisms that Control Energy Homeostasis. Cell Metabolism 2018, 27: 1168-1175. PMID: 29874565, DOI: 10.1016/j.cmet.2018.05.015.Peer-Reviewed Original Research
2017
Cannabis in fat: high hopes to treat obesity
Hawkins MN, Horvath TL. Cannabis in fat: high hopes to treat obesity. Journal Of Clinical Investigation 2017, 127: 3918-3920. PMID: 29035279, PMCID: PMC5663345, DOI: 10.1172/jci97042.Peer-Reviewed Original ResearchConceptsCannabinoid receptor type 1Body weightNovel peripheral targetsReduced body weightSystemic metabolic changesAdipocyte-specific deletionReceptor type 1Sympathetic toneTotal adiposityCNS effectsPeripheral mechanismsSystemic metabolismPeripheral targetsAdipocyte physiologyAdipose tissueType 1Metabolic changesMetabolic profileEnergy metabolismMetabolismAdiposityObesityCausal relationshipMiceMacrophagesRegulation 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
2016
Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability
García-Cáceres C, Quarta C, Varela L, Gao Y, Gruber T, Legutko B, Jastroch M, Johansson P, Ninkovic J, Yi CX, Le Thuc O, Szigeti-Buck K, Cai W, Meyer CW, Pfluger PT, Fernandez AM, Luquet S, Woods SC, Torres-Alemán I, Kahn CR, Götz M, Horvath TL, Tschöp MH. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability. Cell 2016, 166: 867-880. PMID: 27518562, PMCID: PMC8961449, DOI: 10.1016/j.cell.2016.07.028.Peer-Reviewed Original ResearchConceptsBlood-brain barrierSystemic glucose metabolismInsulin receptorGlucose metabolismGlucose uptakeGlial fibrillary acidic proteinBrain glucose uptakePostnatal ablationHypothalamic glucose sensingGlutamate-aspartate transporterFibrillary acidic proteinPositron emission tomographyMelanocortin neuronsKO miceGlucose levelsAstrocyte morphologyNormal responseEmission tomographyGlucose-induced activationAcidic proteinAspartate transporterCircuit connectivityInsulinGlucose availabilityMitochondrial function
2015
Mitochondrial ROS Signaling in Organismal Homeostasis
Shadel GS, Horvath TL. Mitochondrial ROS Signaling in Organismal Homeostasis. Cell 2015, 163: 560-569. PMID: 26496603, PMCID: PMC4634671, DOI: 10.1016/j.cell.2015.10.001.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesOrganismal homeostasisMitochondrial ROS signalingMitochondrial reactive oxygen speciesAdaptive physiological responsesROS signalingCellular differentiationMitochondrial oxygen consumptionOxidative phosphorylationPhysiological responsesOxygen speciesCentral roleHomeostasisEukaryotesOrganic fuel moleculesPhosphorylationMitochondriaMoleculesSignalingSpeciesATPDifferentiationPathwayGreater understandingRoleAgRP Neurons Regulate Bone Mass
Kim JG, Sun BH, Dietrich MO, Koch M, Yao GQ, Diano S, Insogna K, Horvath TL. AgRP Neurons Regulate Bone Mass. Cell Reports 2015, 13: 8-14. PMID: 26411686, PMCID: PMC5868421, DOI: 10.1016/j.celrep.2015.08.070.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusBone DensityBone Diseases, MetabolicFemurGene Expression RegulationHomeostasisHypothalamusIon ChannelsLeptinMaleMiceMice, KnockoutMitochondrial ProteinsNeuronsNorepinephrinePhenotypePropranololReceptors, Adrenergic, betaReceptors, LeptinSignal TransductionSirtuin 1TibiaUncoupling Protein 2ConceptsAgRP neuronsCell-autonomous deletionSignificant regulatory roleAgRP neuronal functionBone massLeptin receptor deletionSkeletal bone metabolismTransgenic animalsRegulatory roleGene deletionBone homeostasisDeletionNeuronal functionPostnatal deletionSympathetic toneReceptor deletionArcuate nucleusLeptin actionBone metabolismSkeletal metabolismMultiple linesNeuronsMiceMetabolismCircuit integrity
2014
Hypothalamic Sidedness in Mitochondrial Metabolism
Toth I, Kiss DS, Goszleth G, Bartha T, Frenyo LV, Naftolin F, Horvath TL, Zsarnovszky A. Hypothalamic Sidedness in Mitochondrial Metabolism. Reproductive Sciences 2014, 21: 1492-1498. PMID: 24740989, DOI: 10.1177/1933719114530188.Peer-Reviewed Original Research
2013
Uncovering Novel Roles of Nonneuronal Cells in Body Weight Homeostasis and Obesity
Chowen JA, Argente J, Horvath TL. Uncovering Novel Roles of Nonneuronal Cells in Body Weight Homeostasis and Obesity. Endocrinology 2013, 154: 3001-3007. PMID: 23798599, PMCID: PMC3749483, DOI: 10.1210/en.2013-1303.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesEnergy MetabolismEpendymaHomeostasisHumansHypothalamusMicrogliaObesityConceptsGlial cellsDiverse functionsNovel rolePhysiological functionsNumerous pathologiesPhysiological regulationNonneuronal cellsBody weight homeostasisCentral nervous systemSecondary complicationsWeight homeostasisCellsPathophysiological responsesSystemic metabolismMetabolic controlNervous systemVast lackPoor nutritionStructural supportNeuroendocrine researchObesityAreas of neuroscienceRecent advancesHeterogeneous classRole
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 riseSirtuin 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 process
2011
Effects 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
2008
Brain circuits regulating energy homeostasis
Abizaid A, Horvath TL. Brain circuits regulating energy homeostasis. Peptides 2008, 149: 3-10. PMID: 18514925, PMCID: PMC2605273, DOI: 10.1016/j.regpep.2007.10.006.Peer-Reviewed Original Research
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 mechanismMachineryIntakeHormone
2006
The unfolding cannabinoid story on energy homeostasis: central or peripheral site of action?
Horvath TL. The unfolding cannabinoid story on energy homeostasis: central or peripheral site of action? International Journal Of Obesity 2006, 30: s30-s32. PMID: 16570102, DOI: 10.1038/sj.ijo.0803275.Peer-Reviewed Original ResearchConceptsBlood-brain barrierCB1 receptor antagonistCentral endocannabinoid systemBody weight regulationWhite adipose tissueCentral nervous systemMesolimbic reward circuitryObserved beneficial effectsEnergy metabolism regulationAnorectic effectPeripheral actionsReceptor antagonistEndocannabinoid systemCB1 antagonistCB1 receptorsBrain sitesCannabinoid actionFood intakeHuman trialsPeripheral tissuesMetabolic disordersWeight regulationAdipose tissueNervous systemPharmaceutical approaches
2005
Obesity and the Neuroendocrine Control of Energy Homeostasis: The Role of Spontaneous Locomotor Activity 1
Castañeda TR, Jürgens H, Wiedmer P, Pfluger P, Diano S, Horvath TL, Tang-Christensen M, Tschöp MH. Obesity and the Neuroendocrine Control of Energy Homeostasis: The Role of Spontaneous Locomotor Activity 1. Journal Of Nutrition 2005, 135: 1314-1319. PMID: 15867332, DOI: 10.1093/jn/135.5.1314.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnergy MetabolismGhrelinHomeostasisHumansMotor ActivityNeurosecretory SystemsObesityPeptide HormonesConceptsSpontaneous physical activityWidespread sedentary lifestylesIntolerable side effectsPrevalence of obesityFat mass accumulationCause of deathUrgent global health threatGlobal health threatSafe therapyFat massPharmacological reductionPhysical activitySedentary lifestyleSide effectsEnergy intakeNeuroendocrine factorsNeuroendocrine controlEnergy homeostasisObesityHealth threatMajor predictorActivity 1Molecular mechanismsLow levelsMajor contributor