2012
Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes
Fuente-Martín E, García-Cáceres C, Granado M, de Ceballos ML, Sánchez-Garrido MÁ, Sarman B, Liu ZW, Dietrich MO, Tena-Sempere M, Argente-Arizón P, Díaz F, Argente J, Horvath TL, Chowen JA. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. Journal Of Clinical Investigation 2012, 122: 3900-3913. PMID: 23064363, PMCID: PMC3484452, DOI: 10.1172/jci64102.Peer-Reviewed Original ResearchConceptsGlial structural proteinsPathology of obesityHypothalamic proopiomelanocortin (POMC) neuronsGlial cell activityOffspring of mothersHigh-fat dietActivity of neuronsExpression of glucoseProopiomelanocortin neuronsHypothalamic astrocytesGlial cellsBody weightSynaptic efficacyGlutamate transportersNeuronal functionCell activityLeptinGlucose uptakeMetabolic statusElectrical activityMetabolic signalsNeuronsAppetiteGlucose transporterKey regulator
2011
High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons
Klöckener T, Hess S, Belgardt BF, Paeger L, Verhagen LA, Husch A, Sohn JW, Hampel B, Dhillon H, Zigman JM, Lowell BB, Williams KW, Elmquist JK, Horvath TL, Kloppenburg P, Brüning JC. High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons. Nature Neuroscience 2011, 14: 911-918. PMID: 21642975, PMCID: PMC3371271, DOI: 10.1038/nn.2847.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAge FactorsAnimalsAnimals, NewbornBlood GlucoseBody WeightCalorimetryDietary FatsDose-Response Relationship, DrugEatingEnzyme InhibitorsEnzyme-Linked Immunosorbent AssayFemaleGene Expression RegulationGlucose Tolerance TestGreen Fluorescent ProteinsHypoglycemic AgentsIn Vitro TechniquesInjections, IntraventricularInsulinLeptinMaleMiceMice, Inbred C57BLMice, TransgenicNeuronsObesityPatch-Clamp TechniquesPhosphatidylinositol 3-KinasesReceptor, InsulinRNA, MessengerSignal TransductionSteroidogenic Factor 1Time FactorsTolbutamideVentromedial Hypothalamic NucleusEffects 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
2010
Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity
Horvath TL, Sarman B, García-Cáceres C, Enriori PJ, Sotonyi P, Shanabrough M, Borok E, Argente J, Chowen JA, Perez-Tilve D, Pfluger PT, Brönneke HS, Levin BE, Diano S, Cowley MA, Tschöp MH. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 14875-14880. PMID: 20679202, PMCID: PMC2930476, DOI: 10.1073/pnas.1004282107.Peer-Reviewed Original ResearchConceptsHigh-fat dietSynaptic input organizationReactive gliosisPOMC neuronsDIO ratsDR ratsArcuate nucleusMelanocortin systemPOMC cellsNeuropeptide Y cellsInput organizationLoss of synapsesDiet-induced obesityBlood-brain barrierHFD-fed animalsDIO animalsAnorexigenic proopiomelanocortinGlial ensheathmentSynaptic organizationInhibitory inputsLean ratsDR animalsNeuronal circuitsCell bodiesGliosis
2008
N-acylphosphatidylethanolamine, a Gut- Derived Circulating Factor Induced by Fat Ingestion, Inhibits Food Intake
Gillum MP, Zhang D, Zhang XM, Erion DM, Jamison RA, Choi C, Dong J, Shanabrough M, Duenas HR, Frederick DW, Hsiao JJ, Horvath TL, Lo CM, Tso P, Cline GW, Shulman GI. N-acylphosphatidylethanolamine, a Gut- Derived Circulating Factor Induced by Fat Ingestion, Inhibits Food Intake. Cell 2008, 135: 813-824. PMID: 19041747, PMCID: PMC2643061, DOI: 10.1016/j.cell.2008.10.043.Peer-Reviewed Original ResearchConceptsFood intakeInhibits food intakeTreatment of obesityNovel therapeutic targetCentral nervous systemUnknown physiological significanceFat ingestionCirculating factorsN-acylphosphatidylethanolaminePlasma lipidsIntracerebroventricular infusionPhysiologic dosesSystemic administrationTherapeutic targetBody weightNervous systemIngested fatSmall intestineIntakeTaste aversionInfusionPhysiological significanceNanomolar amountsObesityHypothalamus
2007
Diet-Induced Leptin Resistance: The Heart of the Matter
Tschöp M, Hui DY, Horvath TL. Diet-Induced Leptin Resistance: The Heart of the Matter. Endocrinology 2007, 148: 921-923. PMID: 17303671, DOI: 10.1210/en.2006-1708.Peer-Reviewed Original Research