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
IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2
Goldberg EL, Shchukina I, Youm YH, Ryu S, Tsusaka T, Young KC, Camell CD, Dlugos T, Artyomov MN, Dixit VD. IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2. Cell Metabolism 2021, 33: 2277-2287.e5. PMID: 34473956, PMCID: PMC9067336, DOI: 10.1016/j.cmet.2021.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAgingAnimalsImmunity, InnateInterleukin-33LungLymphocytesMiceMice, Inbred C57BLConceptsOld miceType 2 innate lymphoid cellsInnate lymphoid cellsTissue-resident cellsCore body temperatureAdoptive transferIL-33ILC2 numbersTissue inflammationAged miceImmunometabolic responsesMetabolic impairmentLymphoid cellsDietary restrictionImmune systemILC2Functional defectsMiceBody temperatureFailureCellsInflammationTranscriptomic analysisInfectionStress response
2020
Dietary Regulation of Immunity
Lee AH, Dixit VD. Dietary Regulation of Immunity. Immunity 2020, 53: 510-523. PMID: 32937152, PMCID: PMC7491384, DOI: 10.1016/j.immuni.2020.08.013.Peer-Reviewed Original ResearchConceptsDietary intakeOrganismal metabolismRestoration of homeostasisRegulation of glucoseMacronutrient intakeImmune regulationImmunological functionsImmunological responseImmunometabolic responsesMitochondrial respirationImmune systemInsulin actionDietary regulationProtein metabolismTissue functionIntakeDietary surplusRegulationVital functionsImmunityMetabolismHealthspanLeukocytesCheckpointHomeostasis
2019
Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis
Camell CD, Günther P, Lee A, Goldberg EL, Spadaro O, Youm YH, Bartke A, Hubbard GB, Ikeno Y, Ruddle NH, Schultze J, Dixit VD. Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis. Cell Metabolism 2019, 30: 1024-1039.e6. PMID: 31735593, PMCID: PMC6944439, DOI: 10.1016/j.cmet.2019.10.006.Peer-Reviewed Original ResearchConceptsAge-associated B cellsFat-associated lymphoid clustersB cellsAdipose tissue leukocytesB-cell depletionB cell accumulationBody temperature maintenanceFALC formationVisceral adiposityCell depletionNLRP3 inflammasomeFemale miceLymphoid clustersMetabolic dysfunctionIL-1Metabolic impairmentIL-1RTissue leukocytesCell accumulationMetabolic homeostasisUnique populationLipolysisCellsTemperature maintenanceAdiposity
2017
Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Ferrandino G, Kaspari RR, Spadaro O, Reyna-Neyra A, Perry RJ, Cardone R, Kibbey RG, Shulman GI, Dixit VD, Carrasco N. Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e9172-e9180. PMID: 29073114, PMCID: PMC5664516, DOI: 10.1073/pnas.1707797114.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseDe novo lipogenesisAdipose tissue lipolysisHepatic insulin resistanceThyroid hormonesHypothyroid miceImpaired suppressionInsulin resistanceTissue lipolysisInsulin secretionHigh thyroid-stimulating hormone levelsRegulation of THThyroid-stimulating hormone levelsLipid utilizationFatty liver diseaseSerum glucose levelsEndogenous glucose productionLow thyroid hormoneFatty acidsHepatic lipid utilizationLiver diseaseSevere hypothyroidismHormone levelsProfound suppressionGlucose levelsInflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing
Camell CD, Sander J, Spadaro O, Lee A, Nguyen KY, Wing A, Goldberg EL, Youm YH, Brown CW, Elsworth J, Rodeheffer MS, Schultze JL, Dixit VD. Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature 2017, 550: 119-123. PMID: 28953873, PMCID: PMC5718149, DOI: 10.1038/nature24022.Peer-Reviewed Original ResearchAdipocytesAdipose TissueAgingAnimalsCaspase 1CatecholaminesGene Expression ProfilingGene Expression RegulationGrowth Differentiation Factor 3InflammasomesLipaseLipolysisMacrophagesMiceMonoamine OxidaseMonoamine Oxidase InhibitorsNLR Family, Pyrin Domain-Containing 3 ProteinNorepinephrineSterol EsteraseIGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge
Spadaro O, Camell CD, Bosurgi L, Nguyen KY, Youm YH, Rothlin CV, Dixit VD. IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge. Cell Reports 2017, 19: 225-234. PMID: 28402847, PMCID: PMC5513500, DOI: 10.1016/j.celrep.2017.03.046.Peer-Reviewed Original ResearchConceptsMacrophage activationM2-like stateHelminth Nippostrongylus brasiliensisNormal insulin sensitivityAdipose tissue macrophagesHigh-fat dietM2-like macrophage activationTyrosine hydroxylase expressionM2-like macrophagesMacrophage activation phenotypeInsulin resistanceInsulin sensitivityHydroxylase expressionImmunometabolic responsesElevated adipositySpecific cytokinesKnockout miceAdipose tissueMacrophage phenotypeMyeloid cellsNippostrongylus brasiliensisTissue macrophagesPhagocytic activityIGF1 receptorCold challengeCarnitine acetyltransferase (CRAT) expression in macrophages is dispensable for nutrient stress sensing and inflammation
Goldberg EL, Dixit VD. Carnitine acetyltransferase (CRAT) expression in macrophages is dispensable for nutrient stress sensing and inflammation. Molecular Metabolism 2017, 6: 219-225. PMID: 28180063, PMCID: PMC5279934, DOI: 10.1016/j.molmet.2016.12.008.Peer-Reviewed Original ResearchConceptsNutrient stressFatty acid oxidationAcyl-CoA poolMacrophage energy metabolismAcid oxidationMetabolic stressorsMyeloid lineage cellsStress sensingSwitch mechanismMetabolic homeostasisLineage cellsEnergy metabolismImportant unanswered questionsMuscle cellsHomeostasisCRATHigh-fat diet-induced obesityAcetyltransferase expressionDiet-induced obesityGlucose homeostasisTissue leukocytosisMacrophagesCellsLittermate controlsUnanswered questions
2015
Editorial: “Crowning” eosinophils in adipose tissue: does location matter?
Goldberg EL, Dixit VD. Editorial: “Crowning” eosinophils in adipose tissue: does location matter? Journal Of Leukocyte Biology 2015, 98: 451-452. PMID: 26429777, DOI: 10.1189/jlb.3ce0415-178rr.Peer-Reviewed Original ResearchAdipose tissue as an immunological organ
Grant RW, Dixit VD. Adipose tissue as an immunological organ. Obesity 2015, 23: 512-518. PMID: 25612251, PMCID: PMC4340740, DOI: 10.1002/oby.21003.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAdipose TissueDiabetes Mellitus, Type 2HumansImmunity, InnateInflammationMetabolic SyndromeObesityConceptsAdipose tissueImmunological organActive immunological organNumerous immune cellsObesity-associated comorbiditiesImmune cell subtypesAdaptive immune responsesType 2 diabetesCertain infectious diseasesWhole-body metabolismMetabolic syndromeObese subjectsChronic inflammationImmunological aspectsInsulin resistanceTissue inflammationObesity influencesImmune cellsImmune surveillanceT cellsImmune responseTissue leukocytosisPubMed searchB cellsHost defense
2014
Adipose Tissue Macrophages Promote Myelopoiesis and Monocytosis in Obesity
Nagareddy PR, Kraakman M, Masters SL, Stirzaker RA, Gorman DJ, Grant RW, Dragoljevic D, Hong ES, Abdel-Latif A, Smyth SS, Choi SH, Korner J, Bornfeldt KE, Fisher EA, Dixit VD, Tall AR, Goldberg IJ, Murphy AJ. Adipose Tissue Macrophages Promote Myelopoiesis and Monocytosis in Obesity. Cell Metabolism 2014, 19: 821-835. PMID: 24807222, PMCID: PMC4048939, DOI: 10.1016/j.cmet.2014.03.029.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBone MarrowCarrier ProteinsCell ProliferationHumansInflammasomesInterleukin-1betaMacrophagesMaleMiceMice, Inbred C57BLMonocytesMyeloid Differentiation Factor 88MyelopoiesisNeutrophilsNLR Family, Pyrin Domain-Containing 3 ProteinObesityReceptors, Interleukin-1Toll-Like Receptor 4ConceptsAT macrophagesInsulin resistanceNLRP3 inflammasome-dependent IL-1β productionAdipose tissueMyeloid progenitorsTLR4/MyD88Infiltration of macrophagesBone marrow myeloid progenitorsIL-1β productionS100A8/A9IL-1 receptorMarrow myeloid progenitorsProduction of monocytesAT inflammationLean recipientsNLRP3-ILTLR4 ligandIL-1βMurine modelMyeloid progenitor proliferationProminent monocytosisObesityMonocytosisWeight lossProgenitor proliferationInactivation of C/ebp Homologous Protein-driven Immune-Metabolic Interactions Exacerbate Obesity and Adipose Tissue Leukocytosis*
Grant R, Nguyen KY, Ravussin A, Albarado D, Youm YH, Dixit VD. Inactivation of C/ebp Homologous Protein-driven Immune-Metabolic Interactions Exacerbate Obesity and Adipose Tissue Leukocytosis*. Journal Of Biological Chemistry 2014, 289: 14045-14055. PMID: 24662293, PMCID: PMC4022874, DOI: 10.1074/jbc.m113.545921.Peer-Reviewed Original ResearchConceptsAblation of CHOPChronic caloric excessHigh-fat dietInsulin resistanceFat dietCaloric excessTissue leukocytosisTissue macrophagesChronic positive energy balanceActivation of ILHigher insulin resistanceImportant molecular mediatorAdipose tissue macrophagesCHOP-deficient miceImmune-metabolic interactionsTranscription factor C/EBP homologous proteinC/EBP homologous proteinSensitivity of macrophagesEndoplasmic reticulum stressHealthy obesityFrequency of M1Inflammatory mechanismsMetabolic inflammationImmune activationPositive energy balance