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
MC4R Signaling in Dorsal Raphe Nucleus Controls Feeding, Anxiety, and Depression
Bruschetta G, Jin S, Liu ZW, Kim JD, Diano S. MC4R Signaling in Dorsal Raphe Nucleus Controls Feeding, Anxiety, and Depression. Cell Reports 2020, 33: 108267. PMID: 33053350, DOI: 10.1016/j.celrep.2020.108267.Peer-Reviewed Original ResearchConceptsDorsal raphe nucleusNeuronal activationR neuronsDepressive-like behaviorMajor depressive disorderChemogenetic activationR miceChemogenetic inhibitionRaphe nucleusSerotonin levelsDepressive disorderMood behaviorΑ-MSHDRN infusionsControl feedingMiceWeight lossNeuronsSelective knockdownDepressionBehavioral phenotypesAnxietyActivationFeedingPRCPImpaired 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
2017
DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons
Santoro A, Campolo M, Liu C, Sesaki H, Meli R, Liu ZW, Kim JD, Diano S. DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons. Cell Metabolism 2017, 25: 647-660. PMID: 28190775, PMCID: PMC5366041, DOI: 10.1016/j.cmet.2017.01.003.Peer-Reviewed Original ResearchConceptsPeroxisome proliferator-activated receptorPOMC neuronsLeptin sensitivityHypothalamic pro-opiomelanocortin (POMC) neuronsPro-opiomelanocortin (POMC) neuronsCounter-regulatory responseProliferator-activated receptorMitochondrial sizeFed miceGlucoprivic stimuliNeuronal activationFl/Glucose metabolismMetabolic environmentNeuronsFasted animalsIntracellular mechanismsReduced expressionGlucose responsivenessGreater activationInducible deletionROS productionMiceStrong inhibitionMitochondrial fission regulator
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
2006
Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding
Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, Thurmon JJ, Marinelli M, DiLeone RJ. Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding. Neuron 2006, 51: 801-810. PMID: 16982424, DOI: 10.1016/j.neuron.2006.08.023.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsDopamineEatingFeeding BehaviorGene ExpressionIn Situ Hybridization, FluorescenceIn Vitro TechniquesInfusions, IntravenousLeptinMesencephalonMiceMice, Inbred C57BLMotor ActivityNeuronsPhosphorylationRatsRats, Sprague-DawleyReceptors, Cell SurfaceReceptors, LeptinRNA InterferenceRNA, MessengerSignal TransductionSTAT3 Transcription FactorVentral Tegmental AreaConceptsVentral tegmental areaVTA dopamine neuronsDopamine neuronsFood intakePeripheral metabolic signalsNormal food intakeMidbrain dopamine neuronsLeptin receptor signalingLeptin hormoneTegmental areaLEPR expressionLeptin receptor functionLocomotor activityPalatable foodDirect administrationReceptor functionFiring rateReceptor signalingDirect actionNeuronsLEPR mRNAFunctional evidenceLeptinRNAi-mediated knockdownMetabolic signals