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
Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity
Dietrich MO, Antunes C, Geliang G, Liu ZW, Borok E, Nie Y, Xu AW, Souza DO, Gao Q, Diano S, Gao XB, Horvath TL. Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity. Journal Of Neuroscience 2010, 30: 11815-11825. PMID: 20810901, PMCID: PMC2965459, DOI: 10.1523/jneurosci.2234-10.2010.Peer-Reviewed Original ResearchConceptsFood intakeMelanocortin systemAgRP neuronal activityAnorexigenic POMC neuronsHypothalamic melanocortin systemAction of SIRT1Negative energy balanceAgRP neuronsPOMC neuronsCre-lox technologyInhibitory toneMC4R antagonistFat massLean massSynaptic inputsNeuronal activityNeuronal firingAdult miceBody weightSIRT1 inhibitorSynaptic plasticityCalorie restrictionMelanocortin receptorsSIRT1 activityBody metabolismUncoupling 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