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 Research
2023
When 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 findingsMetabolismObesityDiabetesTherapy
2022
The 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 expressionAdipokinesObesityIFNCaloric 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 formationKetogenic 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
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 functionsImmunityMetabolismHealthspanLeukocytesCheckpointHomeostasis
2019
Gaining Weight: Insulin-Eating Islet Macrophages
Spadaro O, Dixit VD. Gaining Weight: Insulin-Eating Islet Macrophages. Immunity 2019, 50: 13-15. PMID: 30650372, DOI: 10.1016/j.immuni.2018.12.026.Peer-Reviewed Original Research
2017
Energy Sparing Orexigenic Inflammation of Obesity
Lee A, Dixit VD. Energy Sparing Orexigenic Inflammation of Obesity. Cell Metabolism 2017, 26: 10-12. PMID: 28683278, DOI: 10.1016/j.cmet.2017.06.013.Peer-Reviewed Original Researchβ-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares
Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.Peer-Reviewed Original ResearchConceptsKetogenic dietGouty flaresΒ-hydroxybutyrateMajor risk factorAnti-inflammatory moleculesNLRP3-dependent mannerAlternate metabolic fuelsGout flaresJoint destructionIL-1βIntense painInterleukin-1βNLRP3 inflammasomeRisk factorsInflammatory neutrophilsBacterial infectionsNeutrophilsNLRP3Immune defenseGoutMetabolic fuelsBHBS100A9 fibrilsDietPain
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 depotsThe ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease
Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D'Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nature Medicine 2015, 21: 263-269. PMID: 25686106, PMCID: PMC4352123, DOI: 10.1038/nm.3804.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 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