2024
Defying “IL-11ness” by inhibiting inflammation: Strategy for health and longevity
Kim H, Dixit V. Defying “IL-11ness” by inhibiting inflammation: Strategy for health and longevity. Cell Metabolism 2024, 36: 1911-1913. PMID: 39232279, DOI: 10.1016/j.cmet.2024.08.003.Peer-Reviewed Original ResearchAdiposity, 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 programsWhen a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging
Mihaylova M, Chaix A, Delibegovic M, Ramsey J, Bass J, Melkani G, Singh R, Chen Z, Ja W, Shirasu-Hiza M, Latimer M, Mattison J, Thalacker-Mercer A, Dixit V, Panda S, Lamming D. When a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging. Cell Metabolism 2023, 35: 1114-1131. PMID: 37392742, PMCID: PMC10528391, DOI: 10.1016/j.cmet.2023.06.008.Peer-Reviewed Original ResearchConceptsCalorie restrictionHealthy agingEpidemic of obesityTime-restricted feedingWhole-body metabolismMacronutrient sourcesAge-associated diseasesCardiovascular diseaseNovel therapiesMetabolic effectsMacronutrient compositionDiet qualityMedicine approachNIH workshopCaloriesMetabolic responseDiseaseMediators of metabolismDietary compositionMolecular mechanismsRecent findingsMetabolismObesityDiabetesTherapyInnate immune cell-intrinsic ketogenesis is dispensable for organismal metabolism and age-related inflammation
Goldberg E, Letian A, Dlugos T, Leveau C, Dixit V. Innate immune cell-intrinsic ketogenesis is dispensable for organismal metabolism and age-related inflammation. Journal Of Biological Chemistry 2023, 299: 103005. PMID: 36775129, PMCID: PMC10025153, DOI: 10.1016/j.jbc.2023.103005.Peer-Reviewed Original ResearchConceptsAge-related inflammationKetone bodiesOrganismal metabolismMyeloid cellsChronic low-grade inflammationKetogenic diet feedingLow-grade inflammationHigh-fat dietAbundant ketone bodyGlucose toleranceNLRP3 inflammasomeDiet feedingGlucose homeostasisMouse modelBody weightInflammationMetabolic checkpointOnly organConditional ablationTerminal enzymeΒ-hydroxybutyrateFunctional targetingMethylglutaryl-CoA lyaseKetogenesisModest effect
2022
Unified total synthesis of the limonoid alkaloids: Strategies for the de novo synthesis of highly substituted pyridine scaffolds
Schuppe A, Liu Y, Gonzalez-Hurtado E, Zhao Y, Jiang X, Ibarraran S, Huang D, Wang E, Lee J, Loria J, Dixit V, Li X, Newhouse T. Unified total synthesis of the limonoid alkaloids: Strategies for the de novo synthesis of highly substituted pyridine scaffolds. Chem 2022, 8: 2856-2887. PMID: 37396824, PMCID: PMC10311986, DOI: 10.1016/j.chempr.2022.09.012.Peer-Reviewed Original ResearchThe matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
Ryu S, Sidorov S, Ravussin E, Artyomov M, Iwasaki A, Wang A, Dixit VD. The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity 2022, 55: 1609-1626.e7. PMID: 35963236, PMCID: PMC9474643, DOI: 10.1016/j.immuni.2022.07.007.Peer-Reviewed Original ResearchConceptsToll-like receptor 4ISG inductionMatricellular proteinPro-inflammatory phenotypeAnti-inflammatory macrophagesInterferon-stimulated gene expressionAdipocyte-specific deletionInhibition of glycolysisImmunometabolic adaptationsMyD88 pathwayReceptor 4Chronic diseasesFunctional declineCaloric restrictionInterferon responseHealth spanMacrophagesInflammationMitochondrial respirationSPARCInductionGene expressionAdipokinesObesityIFNImmune cells use hunger hormones to aid healing
Dixit VD. Immune cells use hunger hormones to aid healing. Nature 2022, 609: 39-40. PMID: 35948678, DOI: 10.1038/d41586-022-02105-z.Peer-Reviewed Original ResearchCaloric 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 roleImmunotherapyMorbidityDesmosterol 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 formationIL-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 ResearchConceptsOld miceType 2 innate lymphoid cellsInnate lymphoid cellsTissue-resident cellsCore body temperatureAdoptive transferIL-33ILC2 numbersTissue inflammationAged miceImmunometabolic responsesMetabolic impairmentLymphoid cellsDietary restrictionImmune systemILC2Functional defectsMiceBody temperatureFailureCellsInflammationTranscriptomic analysisInfectionStress responseKetogenic 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 predictorLungMortalityAgeAdiponectin preserves metabolic fitness during aging
Li N, Zhao S, Zhang Z, Zhu Y, Gliniak CM, Vishvanath L, An YA, Wang MY, Deng Y, Zhu Q, Shan B, Sherwood A, Onodera T, Oz OK, Gordillo R, Gupta RK, Liu M, Horvath TL, Dixit VD, Scherer PE. Adiponectin preserves metabolic fitness during aging. ELife 2021, 10: e65108. PMID: 33904399, PMCID: PMC8099426, DOI: 10.7554/elife.65108.Peer-Reviewed Original ResearchConceptsAdiponectin null miceSystemic insulin sensitivityInsulin sensitivityNull miceAge-related glucoseRole of adiponectinLipid metabolism disordersHigh-fat dietTransgenic mouse modelAdiponectin levelsTissue inflammationMetabolism disordersClinical studiesMouse modelAdiponectinMice displayMetabolic fitnessOverexpression modelPositive associationMiceMedian lifespanHealthspanDirect effectEssential regulatorAging process
2020
Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome
Shchukina I, Bagaitkar J, Shpynov O, Loginicheva E, Porter S, Mogilenko DA, Wolin E, Collins P, Demidov G, Artomov M, Zaitsev K, Sidorov S, Camell C, Bambouskova M, Arthur L, Swain A, Panteleeva A, Dievskii A, Kurbatsky E, Tsurinov P, Chernyatchik R, Dixit VD, Jovanovic M, Stewart SA, Daly MJ, Dmitriev S, Oltz EM, Artyomov MN. Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome. Nature Aging 2020, 1: 124-141. PMID: 34796338, PMCID: PMC8597198, DOI: 10.1038/s43587-020-00002-6.Peer-Reviewed Original ResearchConceptsDNA methylomeAge-associated transcriptional changesPromoters of lowlyDNA methylation profilingHuman classical monocytesCorresponding genesPrimary human cellsTranscriptional changesEpigenetic profilingDNA methylationCpG islandsProteomic alterationsSpecific signaturesHypermethylation eventsMethylation profilingHuman cellsMolecular programmingMethylomeGenesMetabolomics dataProfilingComprehensive characterizationHuman monocytesH3K4me1H3K27me3Dietary 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 functionsImmunityMetabolismHealthspanLeukocytesCheckpointHomeostasisKetogenesis 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 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 maintenanceAdiposityAGING 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 dysfunctionKetogenic diet activates protective γδ T cell responses against influenza virus infection
Goldberg EL, Molony RD, Kudo E, Sidorov S, Kong Y, Dixit VD, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. Science Immunology 2019, 4 PMID: 31732517, PMCID: PMC7189564, DOI: 10.1126/sciimmunol.aav2026.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietIAV infectionT cellsGlobal health care concernHigh-fat ketogenic dietΓδ T cell responsesInfection-associated morbidityLethal IAV infectionT cell responsesInfluenza virus infectionHealth care concernHigh-carbohydrate dietInfluenza diseaseKD feedingVirus infectionNew therapiesAntiviral resistanceHepatic ketogenesisCare concernsCell responsesInfectionBarrier functionDietMetabolic adaptation