2022
Caloric restriction in humans reveals immunometabolic regulators of health span
Spadaro O, Youm Y, Shchukina I, Ryu S, Sidorov S, Ravussin A, Nguyen K, Aladyeva E, Predeus AN, Smith SR, Ravussin E, Galban C, Artyomov MN, Dixit VD. Caloric restriction in humans reveals immunometabolic regulators of health span. Science 2022, 375: 671-677. PMID: 35143297, PMCID: PMC10061495, DOI: 10.1126/science.abg7292.Peer-Reviewed Original ResearchMeSH Keywords1-Alkyl-2-acetylglycerophosphocholine EsteraseAdipose TissueAdultAgingAnimalsCaloric RestrictionDown-RegulationEnergy MetabolismFemaleHumansImmune SystemInflammasomesInflammationLongevityLymphopoiesisMacrophagesMaleMiceMiddle AgedMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinThermogenesisThymus GlandTranscriptomeConceptsCaloric restrictionAge-related inflammationHealth spanAnti-inflammatory responseNLRP3 inflammasome activationEctopic lipidsMetabolic healthInflammasome activationHealthy humansAdipose tissueImmunometabolic effectsFactor acetyl hydrolaseImmune defenseInflammationAcetyl hydrolaseMitochondrial bioenergeticsHumansLife spanLipoatrophyPLA2G7ThymopoiesisMice
2021
Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis
Zhang X, McDonald JG, Aryal B, Canfrán-Duque A, Goldberg EL, Araldi E, Ding W, Fan Y, Thompson BM, Singh AK, Li Q, Tellides G, Ordovás-Montanes J, García Milian R, Dixit VD, Ikonen E, Suárez Y, Fernández-Hernando C. Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2107682118. PMID: 34782454, PMCID: PMC8617522, DOI: 10.1073/pnas.2107682118.Peer-Reviewed Original ResearchConceptsCholesterol biosynthetic intermediatesBiosynthetic intermediatesDependent inflammasome activationSingle-cell transcriptomicsMitochondrial reactive oxygen species productionFoam cell formationMacrophage foam cellsReactive oxygen species productionHuman coronary artery lesionsConversion of desmosterolTranscriptomic analysisMacrophage cholesterol metabolismPhysiological contextOxygen species productionLiver X receptor ligandsApoptosis-associated speck-like proteinRetinoid X receptor activationX receptor ligandsInflammasome activationAtherosclerotic plaquesSpeck-like proteinCholesterol homeostasisMacrophage inflammasome activationKey moleculesCell formation
2016
Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence
Spadaro O, Goldberg EL, Camell CD, Youm YH, Kopchick JJ, Nguyen KY, Bartke A, Sun LY, Dixit VD. Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence. Cell Reports 2016, 14: 1571-1580. PMID: 26876170, PMCID: PMC5992590, DOI: 10.1016/j.celrep.2016.01.044.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAutocrine CommunicationBone Marrow CellsCarrier ProteinsGene Expression RegulationHomeostasisImmunity, InnateImmunologic MemoryInflammasomesInterferon-gammaLongevityMacrophagesMiceMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinReceptor, IGF Type 1Receptors, SomatotropinSignal TransductionSpleenT-LymphocytesConceptsNLRP3 inflammasome activationInflammasome activationImmune senescenceAge-related immune senescenceGrowth hormone receptor deficiencyHigher IFNγ secretionNaive T lymphocytesImmune system homeostasisMyeloid lineage cellsEffector memoryIFNγ secretionInflammasome inhibitionEffector cellsChronic inflammationReceptor deficiencyAdvanced ageAge-related activationSystemic activationT lymphocytesGrowth hormone receptorNLRP3 ligandsInnate immuneSomatotropic axisSystem homeostasisNLRP3
2015
Ketone body beta-hydroxy butyrate deactivates NLRP3 inflammasome in myeloid cells (CAM1P.153)
Goldberg E, Youm Y, Nguyen K, Alnemri E, Dixit V. Ketone body beta-hydroxy butyrate deactivates NLRP3 inflammasome in myeloid cells (CAM1P.153). The Journal Of Immunology 2015, 194: 48.10-48.10. DOI: 10.4049/jimmunol.194.supp.48.10.Peer-Reviewed Original ResearchBeta-hydroxy butyrateInflammasome activationMyeloid cellsNLRP3-dependent inflammasome activationAnti-inflammatory interventionsNLRP3-dependent ILMyeloid lineage cellsShort-chain fatty acidsDependent inflammasome activationKetone body productionFatty acid oxidationBone lossChronic inflammationAge-related diseasesAged miceNLRP3 inflammasomeSterile inflammationChronic diseasesFunctional declineMetabolic diseasesCognitive declineCalorie restrictionChain fatty acidsInflammationLineage cells