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
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 roleImmunotherapyMorbidity
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
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
2018
Loss of Nucleobindin-2 Causes Insulin Resistance in Obesity without Impacting Satiety or Adiposity
Ravussin A, Youm YH, Sander J, Ryu S, Nguyen K, Varela L, Shulman GI, Sidorov S, Horvath TL, Schultze JL, Dixit VD. Loss of Nucleobindin-2 Causes Insulin Resistance in Obesity without Impacting Satiety or Adiposity. Cell Reports 2018, 24: 1085-1092.e6. PMID: 30067966, PMCID: PMC6223120, DOI: 10.1016/j.celrep.2018.06.112.Peer-Reviewed Original ResearchConceptsHigh-fat dietInsulin resistanceFood intakeMetabolic inflammationNucleobindin-2M2-like macrophage polarizationHigh-fat diet feedingWeight lossAdipose tissue macrophagesObesity-associated diseasesNesfatin-1Insulin sensitivityDiet feedingMacrophage polarizationNUCB2 proteinMyeloid cellsTissue macrophagesGlobal deletionClassical M1NUCB2NFκB-dependent mannerWeight gainSatietyIntakeAdiposity
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 levelsEnergy 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 ResearchCarnitine 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
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 depotsAdipose 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 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