2022
Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance
Huang Y, Zhou JH, Zhang H, Canfrán-Duque A, Singh AK, Perry RJ, Shulman G, Fernandez-Hernando C, Min W. Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance. Journal Of Clinical Investigation 2022, 132 PMID: 35202005, PMCID: PMC9057632, DOI: 10.1172/jci148852.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, BrownAnimalsDiet, High-FatDNA, MitochondrialEnergy MetabolismInflammationInsulin ResistanceMiceMice, Inbred C57BLMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinReactive Oxygen SpeciesThermogenesisThioredoxinsConceptsBrown adipose tissueBAT inflammationInsulin resistanceMitochondrial reactive oxygen speciesReactive oxygen speciesAberrant innate immune responsesDiet-induced insulin resistanceSystematic metabolismDiet-induced obesityNLRP3 inflammasome pathwayWhole-body energy metabolismCGAS/STINGInnate immune responseFatty acid oxidationExcessive mitochondrial reactive oxygen speciesMetabolic benefitsImmune responseInflammasome pathwayAdipose tissueInflammationInhibition reversesLipid uptakeLipid metabolismThioredoxin 2Adaptive thermogenesis
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 depotsMacrophage-specific de Novo Synthesis of Ceramide Is Dispensable for Inflammasome-driven Inflammation and Insulin Resistance in Obesity*
Camell CD, Nguyen KY, Jurczak MJ, Christian BE, Shulman GI, Shadel GS, Dixit VD. Macrophage-specific de Novo Synthesis of Ceramide Is Dispensable for Inflammasome-driven Inflammation and Insulin Resistance in Obesity*. Journal Of Biological Chemistry 2015, 290: 29402-29413. PMID: 26438821, PMCID: PMC4705943, DOI: 10.1074/jbc.m115.680199.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBone Marrow CellsCarrier ProteinsCeramidesDiet, High-FatDisease Models, AnimalFatty AcidsFemaleInflammasomesInflammationInsulin ResistanceLipidsMacrophagesMaleMiceMice, TransgenicMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinObesityOxidative StressSerine C-PalmitoyltransferaseConceptsDe novo synthesisNovo synthesisOverexpression of catalaseDietary lipid overloadSynthesis machineryTissue homeostasisCell-specific deletionInflammasome activationAdipose tissue homeostasisNLRP3 inflammasome activationMyeloid cell-specific deletionMetabolic pathwaysCeramide synthesisAlternate metabolic pathwaysCaspase-1 cleavageEnergy homeostasisLipid overloadCeramideLipid metabolismInflammasome-dependent mannerOxidative stressDanger signalsFat diet-induced obesityHomeostasisFatty acids