2022
Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity
Wang Q, Zhang B, Stutz B, Liu ZW, Horvath TL, Yang X. Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity. Science Advances 2022, 8: eabn8092. PMID: 36044565, PMCID: PMC9432828, DOI: 10.1126/sciadv.abn8092.Peer-Reviewed Original ResearchConceptsVentromedial hypothalamusWhite adipose tissueVMH neuronsAdipose tissueBody weightLipid metabolismRapid weight gainCounterregulatory responsesSympathetic activitySympathetic innervationAdipocyte hypertrophyTissue lipolysisNeuronal excitabilityFood intakePhysical activityObesity phenotypesGenetic ablationWeight gainHomeostatic set pointEnergy expenditureNeuronsInnervationLipolysisSignificant changesCellular sensors
2018
From white to beige: a new hypothalamic pathway
Miletta MC, Horvath TL. From white to beige: a new hypothalamic pathway. EMBO Reports 2018, 19: embr201845928. PMID: 29581171, PMCID: PMC5891399, DOI: 10.15252/embr.201845928.Peer-Reviewed Original ResearchConceptsVentromedial hypothalamusSympathetic nervous system outflowSubcutaneous white adipose tissueWhite adipose tissueSympathetic outflowHypothalamic pathwaysHomeostatic signalsAdipose tissueBeige fatBeige adipocytesNeuronal circuitsEnergy homeostasisFat tissueSystem outflowNeuronsMetabolic roleTissueActivationCross talkRegulatory pathwaysBeigingObesityHypothalamusVMHPathway
2014
A temperature hypothesis of hypothalamus-driven obesity.
Horvath TL, Stachenfeld NS, Diano S. A temperature hypothesis of hypothalamus-driven obesity. The Yale Journal Of Biology And Medicine 2014, 87: 149-58. PMID: 24910560, PMCID: PMC4031788.Commentaries, Editorials and LettersConceptsTreatment of obesityWhite adipose tissueEtiology of obesityBrain temperature controlHealth care systemSustained obesityObesity developmentPeripheral tissuesMetabolic disordersLarge financial burdenObesityAdipose tissueMedical strategiesExcess fatMetabolic centersPsychological symptomsLength of lifeCare systemFinancial burdenMetabolic stateTissueVast majorityPatientsEtiologySymptoms
2012
Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons
Dietrich MO, Horvath TL. Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons. Nature Reviews Drug Discovery 2012, 11: 675-691. PMID: 22858652, DOI: 10.1038/nrd3739.Peer-Reviewed Original ResearchConceptsNPY/AgRP neuronsNegative energy balanceSevere side effectsAgRP neuronsPOMC neuronsPositive energy balanceChronic disordersPeripheral tissuesReactive oxygen speciesSide effectsLong-term positive energy balanceCalorie restrictionAnti-obesity drug developmentBehavioral interventionsIntense behavioral interventionsPro-opiomelanocortin (POMC) neuronsChronic metabolic disorderLong-term treatmentWhite adipose tissueAlternative therapeutic approachAnti-obesity therapiesPromotion of satietyNew drug therapiesPopulations of neuronsHigher brain functions
2010
Uncoupling Protein-2 Decreases the Lipogenic Actions of Ghrelin
Andrews ZB, Erion DM, Beiler R, Choi CS, Shulman GI, Horvath TL. Uncoupling Protein-2 Decreases the Lipogenic Actions of Ghrelin. Endocrinology 2010, 151: 2078-2086. PMID: 20189996, PMCID: PMC2869261, DOI: 10.1210/en.2009-0850.Peer-Reviewed Original ResearchConceptsBody weight gainGhrelin treatmentWeight gainLipogenic actionsBody weightFat oxidationFat metabolismChronic ghrelin treatmentDaily ip injectionsWhite adipose tissueNegative energy balanceCalorie restriction modelOsmotic minipumpsIP injectionBody fatGhrelinAdipose tissueMiceReactive oxygen speciesExact mechanismUCP2 mRNALipogenesisProtein 2Oxygen speciesTreatment
2007
Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation
Plum L, Rother E, Münzberg H, Wunderlich FT, Morgan DA, Hampel B, Shanabrough M, Janoschek R, Könner AC, Alber J, Suzuki A, Krone W, Horvath TL, Rahmouni K, Brüning JC. Enhanced Leptin-Stimulated Pi3k Activation in the CNS Promotes White Adipose Tissue Transdifferentiation. Cell Metabolism 2007, 6: 431-445. PMID: 18054313, DOI: 10.1016/j.cmet.2007.10.012.Peer-Reviewed Original ResearchConceptsWhite adipose tissueSympathetic nerve activityBrown adipose tissuePI3k activationAdipose tissueLeptin-deficient ob/obOb/ob miceUnaltered body weightEnergy expenditureOb/obLeptin-sensitive neuronsNerve activityEndogenous leptinOb miceBody weightUCP1 expressionWAT morphologyEnergy homeostasisLeptinSkeletal muscleMicePTEN ablationSignaling pathwaysMitochondrial contentDirect genetic evidence
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