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
2011
Obesity is associated with hypothalamic injury in rodents and humans
Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW. Obesity is associated with hypothalamic injury in rodents and humans. Journal Of Clinical Investigation 2011, 122: 153-162. PMID: 22201683, PMCID: PMC3248304, DOI: 10.1172/jci59660.Peer-Reviewed Original ResearchConceptsHigh-fat dietHFD feedingMediobasal hypothalamusPeripheral tissuesRodent modelsBody weight controlHypothalamic arcuate nucleusSubstantial weight gainConsequences of obesityNeuron injuryHypothalamic injuryNeuronal injuryNeuroprotective mechanismsReactive gliosisObese humansHypothalamic areaArcuate nucleusInflammatory signalingBrain areasWeight controlObesityGliosisEnergy homeostasisWeight gainInflammation
2007
A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2
Coppola A, Liu ZW, Andrews ZB, Paradis E, Roy MC, Friedman JM, Ricquier D, Richard D, Horvath TL, Gao XB, Diano S. A Central Thermogenic-like Mechanism in Feeding Regulation: An Interplay between Arcuate Nucleus T3 and UCP2. Cell Metabolism 2007, 5: 21-33. PMID: 17189204, PMCID: PMC1783766, DOI: 10.1016/j.cmet.2006.12.002.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusEatingFastingFeeding BehaviorGreen Fluorescent ProteinsGuanosine DiphosphateHypothalamusIntercellular Signaling Peptides and ProteinsIodide PeroxidaseIon ChannelsMiceMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial ProteinsNeurogliaNeuronsNeuropeptide YProto-Oncogene Proteins c-fosThermogenesisTriiodothyronineUncoupling Protein 2ConceptsUncoupling protein 2Mitochondrial uncoupling protein 2Thyroid hormone productionProtein activityType 2 deiodinaseMitochondrial proliferationNeuropeptide YArcuate nucleusPhysiological roleMitochondrial uncouplingUCP2 activationProtein 2Hormone productionNPY/AgRP neuronsPhysiological significanceActive thyroid hormoneHypothalamic arcuate nucleusHypothalamic neuronal networksGlial cellsRebound feedingAgRP neuronsOrexigenic neuronsDeiodinaseDII activityPeripheral tissues
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