2024
Adiposity, immunity, and inflammation: interrelationships in health and disease: a report from 24th Annual Harvard Nutrition Obesity Symposium, June 2023
Burak M, Stanley T, Lawson E, Campbell S, Lynch L, Hasty A, Domingos A, Dixit V, Hotamışlıgil G, Sheedy F, Dixon A, Brinkley T, Hill J, Donath M, Grinspoon S. Adiposity, immunity, and inflammation: interrelationships in health and disease: a report from 24th Annual Harvard Nutrition Obesity Symposium, June 2023. American Journal Of Clinical Nutrition 2024, 120: 257-268. PMID: 38705359, PMCID: PMC11347817, DOI: 10.1016/j.ajcnut.2024.04.029.Peer-Reviewed Original ResearchLow-grade systemic inflammationChronic low-grade inflammationLocal immune environmentAdipose tissueLow-grade inflammationEffect of obesityObesity Research CenterPro-inflammatory pathwaysOutcome of metabolic diseasesImmune environmentSystemic inflammationHealth and DiseaseTreatment therapiesInflammationMultifaceted effectsDisease severityMetabolic diseasesImmunometabolic diseasesImmunityAdiposeDiseaseReduced disease severityObesityTissueDisrupting cellular homeostasis
2023
IMMUNOMETABOLIC CHECKPOINTS OF INFLAMMAGING
Dixit V. IMMUNOMETABOLIC CHECKPOINTS OF INFLAMMAGING. Innovation In Aging 2023, 7: 140-140. PMCID: PMC10735998, DOI: 10.1093/geroni/igad104.0458.Peer-Reviewed Original ResearchCaloric restrictionAnti-inflammatory effectsAnti-inflammatory responseAge-related functional declineNegative energy balanceTissue-resident macrophagesAge-associated degenerative diseasesThymic involutionMaintenance of homeostasisMetabolic dysfunctionFunctional declineAdipose tissueInflammationResident macrophagesStudy participantsDegenerative diseasesMacrophagesKey hallmarksRNA sequence analysisMitochondrial metabolismHuman physiologyUnique regulatorCellular quiescenceMetabolismTranscriptional programs
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-27 signalling promotes adipocyte thermogenesis and energy expenditure
Wang Q, Li D, Cao G, Shi Q, Zhu J, Zhang M, Cheng H, Wen Q, Xu H, Zhu L, Zhang H, Perry RJ, Spadaro O, Yang Y, He S, Chen Y, Wang B, Li G, Liu Z, Yang C, Wu X, Zhou L, Zhou Q, Ju Z, Lu H, Xin Y, Yang X, Wang C, Liu Y, Shulman GI, Dixit VD, Lu L, Yang H, Flavell RA, Yin Z. IL-27 signalling promotes adipocyte thermogenesis and energy expenditure. Nature 2021, 600: 314-318. PMID: 34819664, DOI: 10.1038/s41586-021-04127-5.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsBariatric SurgeryDisease Models, AnimalEnergy MetabolismFemaleHumansInsulin ResistanceInterleukin-27MaleMiceObesityP38 Mitogen-Activated Protein KinasesPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaReceptors, InterleukinSignal TransductionThermogenesisUncoupling Protein 1ConceptsIL-27Beige adipose tissueAdipose tissueSerum IL-27Diet-induced obesityBariatric surgeryMetabolic morbidityImmunological factorsInsulin resistanceObesity showTherapeutic administrationMetabolic disordersMouse modelObesityPromising targetEnergy expenditureSignaling promotesThermogenesisBody temperatureMetabolic programsImportant roleTissueCritical roleImmunotherapyMorbidityKetogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10: e66522. PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/elife.66522.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietCoronavirus infectionAged miceT cellsHigher systemic inflammationInfected aged miceCOVID-19 severityCOVID-19 infectionActivation of ketogenesisMouse hepatitis virus strain A59Systemic inflammationInflammatory damageInfluenza infectionClinical hallmarkNLRP3 inflammasomeImmune surveillanceAdipose tissuePotential treatmentInfectionMiceStrongest predictorLungMortalityAge
2020
Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue
Goldberg EL, Shchukina I, Asher JL, Sidorov S, Artyomov MN, Dixit VD. Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue. Nature Metabolism 2020, 2: 50-61. PMID: 32694683, PMCID: PMC10150608, DOI: 10.1038/s42255-019-0160-6.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietT cellsAdipose tissue inflammationResident immune cellsVisceral adipose tissueHigher fat compositionReduced adipose tissue inflammationCause obesityMetabolic healthTissue inflammationImmune cellsImmunometabolic responsesProlonged exerciseGlucose homeostasisAdipose tissueInflammationKetone bodiesSingle-cell RNA sequencingLow carbohydrateEnergy homeostasisΒ-hydroxybutyrateFat compositionRNA sequencingCells
2019
AGING INDUCES NLRP3 INFLAMMASOME DEPENDENT ADIPOSE B CELL EXPANSION TO IMPAIR METABOLIC HOMEOSTASIS
Camell C, Dixit V. AGING INDUCES NLRP3 INFLAMMASOME DEPENDENT ADIPOSE B CELL EXPANSION TO IMPAIR METABOLIC HOMEOSTASIS. Innovation In Aging 2019, 3: s106-s106. PMCID: PMC6845598, DOI: 10.1093/geroni/igz038.397.Peer-Reviewed Original ResearchFat-associated lymphoid clustersTissue B cellsB cell expansionAdipose tissueB cellsNLRP3 inflammasomeAdipose tissue immune cellsVisceral white adipose tissueB cell profileB-cell depletionB cell accumulationTissue immune cellsVisceral adipose tissueWhite adipose tissueAged B cellsFALC formationVisceral adiposityCell depletionInduces NLRP3Aged miceImmune cellsInsulin sensitivityFemale miceLymphoid clustersMetabolic dysfunctionNLRP3 Inflammasome regulation of lipolysis in aged adipose tissue
Camell C, Dixit V. NLRP3 Inflammasome regulation of lipolysis in aged adipose tissue. The FASEB Journal 2019, 33: 78.2-78.2. DOI: 10.1096/fasebj.2019.33.1_supplement.78.2.Peer-Reviewed Original ResearchAdipose tissue macrophagesAge-related reductionAdipose triglyceride lipaseHormone-sensitive lipaseVisceral adiposityFree fatty acidsAdipose tissueNLRP3 inflammasome-dependent mannerDeletion of NLRP3Inflammasome-dependent mannerTissue NE concentrationLower exercise capacityAge-related inflammationSympathetic nervous systemDiet-induced obesityImmune-metabolic interactionsCatecholamine-induced lipolysisWhite adipose tissueFull-text articlesCore body temperatureExercise capacityKey lipolytic enzymeMetabolic dysfunctionFunctional declineLeukocyte alterations
2017
IGF1 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 challenge
2015
A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents
Kursawe R, Dixit VD, Scherer PE, Santoro N, Narayan D, Gordillo R, Giannini C, Lopez X, Pierpont B, Nouws J, Shulman GI, Caprio S. A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents. Diabetes 2015, 65: 610-618. PMID: 26718495, PMCID: PMC4764142, DOI: 10.2337/db15-1478.Peer-Reviewed Original ResearchMeSH KeywordsAbdomenAcetyl-CoA CarboxylaseAdipogenesisAdiponectinAdolescentCarrier ProteinsCaspase 1ChildDown-RegulationFatty Acid Synthase, Type IFemaleGene Expression ProfilingGlucose Transporter Type 4HumansInflammasomesInsulin ResistanceInterleukin-1betaIntra-Abdominal FatLeptinLipogenesisLipoprotein LipaseMacrophagesMagnetic Resonance ImagingMaleNLR Family, Pyrin Domain-Containing 3 ProteinObesityPPAR gammaSirtuin 1Sterol Regulatory Element Binding Protein 1Subcutaneous FatToll-Like Receptor 4ConceptsVisceral adipose tissueObese adolescentsInsulin resistanceTissue inflammationNLRP3 inflammasomeAdipose tissueInnate immune cell sensorsAbdominal subcutaneous adipose tissueAbdominal adipose depotsAbdominal fat partitioningAdipogenesis/lipogenesisAdipose tissue inflammationProinflammatory cytokines interleukinInfiltration of macrophagesExpression of CASP1Subcutaneous adipose tissueInflammation markersSAT biopsiesIL-18Macrophage infiltrationVisceral fatCytokines interleukinSAT ratioInsulin sensitivityAdipose depotsNLRP3 inflammasome controls adipose tissue leukocytosis and inflammation during aging (INM6P.331)
Camell C, Youm Y, Nguyen K, Ravussin A, Spadaro O, Dixit V. NLRP3 inflammasome controls adipose tissue leukocytosis and inflammation during aging (INM6P.331). The Journal Of Immunology 2015, 194: 193.5-193.5. DOI: 10.4049/jimmunol.194.supp.193.5.Peer-Reviewed Original ResearchAge-related inflammationAdipose tissueAged miceAntigen-specific T cellsDistinct inflammatory signatureB cell infiltrationSpecific T cellsOld control miceVisceral adipose tissueIL-1β signalingB cell subpopulationsAT inflammationAT macrophagesInflammatory signatureVisceral adiposityImmune defectsChronic inflammationControl miceInsulin resistanceLymphocyte clustersCell infiltrationImmune cellsMetabolic dysfunctionT cellsAge-induced changesAdipose 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 ResearchConceptsAdipose 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 proliferation