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 ResearchMeSH KeywordsAdipose TissueAnimalsBody WeightHypothalamusLipolysisMiceN-AcetylglucosaminyltransferasesObesityConceptsVentromedial 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
2021
Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis
Gómez-Valadés AG, Pozo M, Varela L, Boudjadja MB, Ramírez S, Chivite I, Eyre E, Haddad-Tóvolli R, Obri A, Milà-Guasch M, Altirriba J, Schneeberger M, Imbernón M, Garcia-Rendueles AR, Gama-Perez P, Rojo-Ruiz J, Rácz B, Alonso MT, Gomis R, Zorzano A, D’Agostino G, Alvarez CV, Nogueiras R, Garcia-Roves PM, Horvath TL, Claret M. Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis. Cell Metabolism 2021, 33: 1820-1835.e9. PMID: 34343501, PMCID: PMC8432968, DOI: 10.1016/j.cmet.2021.07.008.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsGTP PhosphohydrolasesHomeostasisLipolysisMiceNeuronsPro-OpiomelanocortinConceptsProtein OPA1Mitochondrial CaMitochondrial cristae architectureAdipose tissue lipolysisKey metabolic sensorPOMC neuronsCellular metabolic adaptationTissue lipolysisCristae architectureMetabolic sensorNutrient availabilityWhite adipose tissue lipolysisAlpha-melanocyte stimulating hormoneGenetic inactivationNovel axisMitochondrial functionOPA1Metabolic adaptationMitochondrial cristaeDramatic alterationsMutant miceProopiomelanocortin neuronsLipolysis controlWAT lipolysisPharmacological blockade
2018
Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis
Aryal B, Singh AK, Zhang X, Varela L, Rotllan N, Goedeke L, Chaube B, Camporez JP, Vatner DF, Horvath TL, Shulman GI, Suárez Y, Fernández-Hernando C. Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis. JCI Insight 2018, 3: e97918. PMID: 29563332, PMCID: PMC5926923, DOI: 10.1172/jci.insight.97918.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAllelesAngiopoietin-Like Protein 4AnimalsAtherosclerosisBody WeightChemokinesCytokinesDiet, High-FatDiet, WesternFatty AcidsGene Expression ProfilingGene Expression RegulationGene Knockout TechniquesGlucoseInsulinIntegrasesIntercellular Signaling Peptides and ProteinsLipid MetabolismLipoprotein LipaseLipoproteinsLiverMaleMiceMice, Inbred C57BLMice, KnockoutMusclesObesityProprotein Convertase 9TriglyceridesConceptsAngiopoietin-like protein 4High-fat dietEctopic lipid depositionLipid depositionGlucose toleranceLipoprotein lipaseShort-term high-fat dietSevere metabolic abnormalitiesProgression of atherosclerosisMajor risk factorTriacylglycerol-rich lipoproteinsFatty acid uptakeAdipose tissue resultsProatherogenic lipoproteinsCardiometabolic diseasesMetabolic abnormalitiesKO miceRisk factorsWhole body lipidMetabolic disordersGlucose metabolismLPL activityAdipose tissueGenetic ablationRapid clearance
2016
CD301b+ Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha
Kumamoto Y, Camporez JP, Jurczak MJ, Shanabrough M, Horvath T, Shulman GI, Iwasaki A. CD301b+ Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha. Immunity 2016, 45: 583-596. PMID: 27566941, PMCID: PMC5033704, DOI: 10.1016/j.immuni.2016.08.002.Peer-Reviewed Original ResearchConceptsMononuclear phagocytesResistin-like molecule αResistin-like molecule alphaSignificant weight lossPositive energy balanceInsulin sensitivityGlucose metabolismAdipose tissueBody weightMultiple organsMultifunctional cytokineBody homeostasisMarked reductionHeterogeneous groupWeight lossPhagocytesMolecule αHomeostasisEnergy balanceRELMαCD301bNormoglycemiaCytokinesMacrophages
2012
Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis
Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Reports 2012, 13: 1079-1086. PMID: 23146889, PMCID: PMC3512417, DOI: 10.1038/embor.2012.174.Peer-Reviewed Original ResearchConceptsGlucose homeostasisEnergy homeostasisPrevalence of obesityWhole-body energy homeostasisBody energy homeostasisAnorectic hormonesAgRP neuronsObese patientsProtein (AgRP) neuronsCentral effectsHypothalamic proopiomelanocortinBody weightInsulin actionLeptinHormonal actionMajor targetInsulin pathwayHomeostasisInsulinNeuronsHormoneBrainLatest findingsEnergy balanceSteady rise
2010
Regulatory T cells in obesity: the leptin connection
Matarese G, Procaccini C, De Rosa V, Horvath TL, La Cava A. Regulatory T cells in obesity: the leptin connection. Trends In Molecular Medicine 2010, 16: 247-256. PMID: 20493774, DOI: 10.1016/j.molmed.2010.04.002.Peer-Reviewed Original ResearchConceptsTreg cellsResident Treg cellsRegulatory T cellsAdipocyte-derived hormonePathogenesis of obesityT cell responsivenessChronic inflammationHypothalamic levelT cellsFood intakeCell responsivenessGlucose homeostasisAdipose tissueTherapeutic interventionsNutritional statusObesityRecent findingsCellsTissueMetabolismInflammationLeptinPathogenesisHormoneIntakeUncoupling 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
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
2003
Endocannabinoids and the regulation of body fat: the smoke is clearing
Horvath TL. Endocannabinoids and the regulation of body fat: the smoke is clearing. Journal Of Clinical Investigation 2003, 112: 323-326. PMID: 12897199, PMCID: PMC166302, DOI: 10.1172/jci19376.Peer-Reviewed Original ResearchUncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice
Horvath TL, Diano S, Miyamoto S, Barry S, Gatti S, Alberati D, Livak F, Lombardi A, Moreno M, Goglia F, Mor G, Hamilton J, Kachinskas D, Horwitz B, Warden CH. Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice. International Journal Of Obesity 2003, 27: 433-442. PMID: 12664076, DOI: 10.1038/sj.ijo.0802257.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBasal MetabolismBlotting, NorthernBlotting, WesternBody TemperatureCarrier ProteinsCholesterol, LDLEnergy IntakeGene Expression RegulationHeart RateInflammationIon ChannelsMaleMembrane Transport ProteinsMiceMice, Inbred C57BLMice, TransgenicMitochondriaMitochondrial ProteinsObesityProteinsUncoupling Protein 2Uncoupling Protein 3ConceptsTransgenic miceFat massLow-density lipoprotein cholesterol levelsHeterozygous miceAgouti obese miceHypothalamic neuropeptide levelsSpontaneous physical activityLipoprotein cholesterol levelsNontransgenic littermate controlsFat pad weightEndotoxin-induced feverWild-type littermatesHuman UCP2Significant differencesMechanism of actionLDL cholesterolControl miceFemale transgenicsNontransgenic littermatesObese miceEndotoxin injectionCholesterol levelsPad weightNeuropeptide levelsFood intakeGhrelin as a potential anti-obesity target.
Horvath TL, Castañeda T, Tang-Christensen M, Pagotto U, Tschöp MH. Ghrelin as a potential anti-obesity target. Current Pharmaceutical Design 2003, 9: 1383-95. PMID: 12769730, DOI: 10.2174/1381612033454748.Peer-Reviewed Original ResearchConceptsPositive energy balancePotential anti-obesity targetEndogenous growth hormone secretagogueEffective pharmacological treatmentAnti-obesity targetGrowth hormone secretagoguesNumerous target tissuesPeptide hormone ghrelinGhrelin antagonistGhrelin actionPharmacological treatmentHormone ghrelinFood intakeHormone secretagoguesPharmacological approachesGhrelinPleiotropic hormoneFat oxidationNeuroendocrine regulationCompensatory mechanismsEnergy homeostasisBlood streamTarget tissuesExact mechanismObesity