2021
Astrocytic lipid metabolism determines susceptibility to diet-induced obesity
Varela L, Kim JG, Fernández-Tussy P, Aryal B, Liu ZW, Fernández-Hernando C, Horvath TL. Astrocytic lipid metabolism determines susceptibility to diet-induced obesity. Science Advances 2021, 7: eabj2814. PMID: 34890239, PMCID: PMC11323787, DOI: 10.1126/sciadv.abj2814.Peer-Reviewed Original ResearchDiet-induced obesityHypothalamic astrocytesPeroxisome proliferator-activated receptor gammaHypothalamic neuronal circuitsProliferator-activated receptor gammaControl of feedingFatty acid homeostasisSystemic glucoseMetabolic milieuGlucose homeostasisBody weightReceptor gammaSynaptic plasticityNeuronal circuitsNutrient sensingLipid metabolismCellular adaptationObesityAstrocytesAcid homeostasisUnidentified roleFA metabolismEnergy metabolismElevated susceptibilityAvailability of FA
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 impairmentBrown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis
Singh AK, Aryal B, Chaube B, Rotllan N, Varela L, Horvath TL, Suárez Y, Fernández-Hernando C. Brown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis. Molecular Metabolism 2018, 11: 59-69. PMID: 29627378, PMCID: PMC6001401, DOI: 10.1016/j.molmet.2018.03.011.Peer-Reviewed Original ResearchConceptsBrown adipose tissueAdipose tissueAbsence of ANGPTL4Lipoprotein metabolismLPL activityShort-term HFD feedingTriglyceride-rich lipoprotein catabolismLipoprotein lipaseRole of ANGPTL4Novel mouse modelAcute cold exposureGlucose toleranceHFD feedingFatty acidsLipoprotein catabolismWhole body lipidGlucose homeostasisMouse modelGlucose metabolismTAG clearanceBAT resultsLipid metabolismANGPTL4Cold exposureFA oxidation
2017
Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control
Ramírez S, Gómez-Valadés AG, Schneeberger M, Varela L, Haddad-Tóvolli R, Altirriba J, Noguera E, Drougard A, Flores-Martínez Á, Imbernón M, Chivite I, Pozo M, Vidal-Itriago A, Garcia A, Cervantes S, Gasa R, Nogueiras R, Gama-Pérez P, Garcia-Roves PM, Cano DA, Knauf C, Servitja JM, Horvath TL, Gomis R, Zorzano A, Claret M. Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control. Cell Metabolism 2017, 25: 1390-1399.e6. PMID: 28591639, DOI: 10.1016/j.cmet.2017.05.010.Peer-Reviewed Original ResearchConceptsMitofusin 1Mitochondrial dynamicsGene expression programsNutrient sensing mechanismsExpression programsMitochondrial architectureMitochondrial oxygen fluxNutrient sensingMitochondrial flexibilityNutrient availabilityPancreatic β-cellsUnrecognized linkDefective insulin secretionOxygen species generationMetabolism controlΒ-cellsSubset of neuronsSystemic glucose metabolismPOMC neuronsCritical sensorsSpecies generationPrecise mechanismGlucose homeostasis
2015
The 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
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 riseFoxO1 Target Gpr17 Activates AgRP Neurons to Regulate Food Intake
Ren H, Orozco IJ, Su Y, Suyama S, Gutiérrez-Juárez R, Horvath TL, Wardlaw SL, Plum L, Arancio O, Accili D. FoxO1 Target Gpr17 Activates AgRP Neurons to Regulate Food Intake. Cell 2012, 149: 1314-1326. PMID: 22682251, PMCID: PMC3613436, DOI: 10.1016/j.cell.2012.04.032.Peer-Reviewed Original ResearchConceptsFood intakeAgRP neuronsG-protein-coupled receptor GPR17Intracerebroventricular injectionHypothalamic neuronsReceptor GPR17Pharmacological modulationGlucose homeostasisNutritional statusTherapeutic potentialMice resultsGenetic ablationNeuronsFoxO1 ablationIntakeSatietyGPR17InsulinExpression profilingAblationPathwayCangrelorObesityLeptinAgonists
2010
Gonadotropin-Releasing Hormone Fibers Contact POMC Neurons in the Hypothalamic Arcuate Nucleus
Sotonyi P, Mezei G, Racz B, Dallman MF, Abizaid A, Horvath TL. Gonadotropin-Releasing Hormone Fibers Contact POMC Neurons in the Hypothalamic Arcuate Nucleus. Reproductive Sciences 2010, 17: 1024-1028. PMID: 20713970, DOI: 10.1177/1933719110378346.Peer-Reviewed Original ResearchConceptsArcuate nucleusGonadotropin-releasing hormone (GnRH) neuronsPOMC cell bodiesEnergy expenditureHypothalamic arcuate nucleusHypothalamic neuronal populationsMelanocyte stimulating hormoneHormone neuronsPOMC neuronsAnorexigenic proopiomelanocortinStimulating hormoneAnatomical proximityAxon terminalsGonadal axisGlucose homeostasisPeripheral signalsNeuronal populationsCell bodiesDirect appositionGnRHEnergy metabolismNeuronsMetabolic stateHormoneProopiomelanocortinRegulatory T cells in obesity: the leptin connection
Matarese G, Procaccini C, De Rosa V, Horvath TL, La Cava A. Regulatory T cells in obesity: the leptin connection. Trends In Molecular Medicine 2010, 16: 247-256. PMID: 20493774, DOI: 10.1016/j.molmed.2010.04.002.Peer-Reviewed Original ResearchConceptsTreg cellsResident Treg cellsRegulatory T cellsAdipocyte-derived hormonePathogenesis of obesityT cell responsivenessChronic inflammationHypothalamic levelT cellsFood intakeCell responsivenessGlucose homeostasisAdipose tissueTherapeutic interventionsNutritional statusObesityRecent findingsCellsTissueMetabolismInflammationLeptinPathogenesisHormoneIntake