2020
AgRP neurons control compulsive exercise and survival in an activity-based anorexia model
Miletta MC, Iyilikci O, Shanabrough M, Šestan-Peša M, Cammisa A, Zeiss CJ, Dietrich MO, Horvath TL. AgRP neurons control compulsive exercise and survival in an activity-based anorexia model. Nature Metabolism 2020, 2: 1204-1211. PMID: 33106687, DOI: 10.1038/s42255-020-00300-8.Peer-Reviewed Original ResearchConceptsAgRP neuronsActivity-based anorexia modelAgRP neuronal activityVivo fiber photometryFood-restricted miceFood-restricted animalsCompulsive exerciseAnorexia modelHypothalamic agoutiNeuropeptide YExercise volumeFood intakeMouse modelNeuronal activityFiber photometryDaily activationNeuronal circuitsPsychiatric conditionsAnorexia nervosaChemogenetic toolsNeuronsLong-term behavioral impactElevated fat contentVoluntary cessationFat content
2014
O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat
Ruan HB, Dietrich MO, Liu ZW, Zimmer MR, Li MD, Singh JP, Zhang K, Yin R, Wu J, Horvath TL, Yang X. O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat. Cell 2014, 159: 306-317. PMID: 25303527, PMCID: PMC4509746, DOI: 10.1016/j.cell.2014.09.010.Peer-Reviewed Original ResearchConceptsAgRP neuronsFundamental cellular processesWhite fatN-acetylglucosamine (O-GlcNAc) modificationOrexigenic AgRP neuronsVoltage-dependent potassium channelsCellular processesGlcNAc transferaseDynamic physiological processesNuclear proteinsWhite adipose tissue browningPhysiological processesAdipose tissue browningDiet-induced obesityPhysiological relevanceTissue browningGenetic ablationBeige cellsEnergy metabolismInsulin resistanceNeuronal excitabilityPotassium channelsAdipose tissueCentral mechanismsNeurons
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
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
2006
Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity
Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Münzberg H, Shanabrough M, Burdakov D, Rother E, Janoschek R, Alber J, Belgardt BF, Koch L, Seibler J, Schwenk F, Fekete C, Suzuki A, Mak TW, Krone W, Horvath TL, Ashcroft FM, Brüning JC. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. Journal Of Clinical Investigation 2006, 116: 1886-1901. PMID: 16794735, PMCID: PMC1481658, DOI: 10.1172/jci27123.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChromonesDietEatingFemaleHypoglycemic AgentsHypothalamusInsulinLeptinMaleMembrane PotentialsMiceMice, KnockoutMorpholinesNeuronsObesityPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoinositide-3 Kinase InhibitorsPotassium ChannelsPro-OpiomelanocortinPTEN PhosphohydrolaseSecond Messenger SystemsTolbutamideConceptsPOMC neuronsATP-sensitive potassium channel activityBasal firing rateHypothalamic proopiomelanocortin (POMC) neuronsElectrical activityKATP channel activationPI3K inhibitor LY294002PTEN knockout micePotassium channel activityK inhibitor LY294002PI3K pathwayProopiomelanocortin neuronsHypothalamic receptorsICV administrationFood intakeKATP channelsKnockout miceMelanocortin systemLeptinFiring rateNeuronsMiceSTAT3 phosphorylationK pathwayInhibitor LY294002