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 ResearchConceptsBrown 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
2020
Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice
Li X, Zhang D, Vatner DF, Goedeke L, Hirabara SM, Zhang Y, Perry RJ, Shulman GI. Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 32584-32593. PMID: 33293421, PMCID: PMC7768680, DOI: 10.1073/pnas.1922169117.Peer-Reviewed Original ResearchConceptsEpididymal white adipose tissueInsulin resistanceAdiponectin treatmentAdipose tissueHigh-fat diet-induced insulin resistanceType 2 diabetes mellitusWhole-body insulin resistanceDiet-induced insulin resistanceSkeletal muscleEctopic lipid storageReverses insulin resistanceInsulin-mediated suppressionMuscle fatty acid oxidationEndogenous glucose productionMuscle insulin resistanceWhite adipose tissueLipoprotein lipase activityMuscle fat oxidationPKCε translocationInsulin-stimulated glucose uptakeFatty acid oxidationTAG uptakeDiabetes mellitusMuscle sensitivityAkt serine phosphorylationEffects of Omega-3 Fatty Acids on Insulin Resistance in an Ovariectomized Mouse Model of Diet-Induced Obesity Treated with Chemotherapy
Ormiston K, Zhang Z, Murphy K, DeVries A, Lustberg M, Andridge R, Orchard T. Effects of Omega-3 Fatty Acids on Insulin Resistance in an Ovariectomized Mouse Model of Diet-Induced Obesity Treated with Chemotherapy. Current Developments In Nutrition 2020, 4: nzaa044_044. PMCID: PMC7257328, DOI: 10.1093/cdn/nzaa044_044.Peer-Reviewed Original ResearchInsulin resistanceLF groupBody weightBlood glucoseHF dietHF groupBody fatHigh-fat diet-induced insulin resistanceOmega-3 fatty acidsDiet-induced insulin resistanceLF diet groupHomeostatic model assessmentHOMA-IR scoreDiet-induced obesityOvariectomized mouse modelDiet-fed miceLow-fat dietHigh-fat dietLower body weightPercent body fatFasted blood glucoseLower scoresChemotherapy injectionsConclusion ChemotherapySerum insulin
2018
Usp25m protease regulates ubiquitin-like processing of TUG proteins to control GLUT4 glucose transporter translocation in adipocytes
Habtemichael EN, Li DT, Alcázar-Román A, Westergaard XO, Li M, Petersen MC, Li H, DeVries SG, Li E, Julca-Zevallos O, Wolenski JS, Bogan JS. Usp25m protease regulates ubiquitin-like processing of TUG proteins to control GLUT4 glucose transporter translocation in adipocytes. Journal Of Biological Chemistry 2018, 293: 10466-10486. PMID: 29773651, PMCID: PMC6036200, DOI: 10.1074/jbc.ra118.003021.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsCarrier ProteinsCell MembraneCells, CulturedGlucoseGlucose Transporter Type 4Hypoglycemic AgentsInsulinIntracellular Signaling Peptides and ProteinsKinesinsMaleMiceMice, Inbred C57BLMotor ActivityProtein TransportProteolysisRatsRats, Sprague-DawleySignal TransductionUbiquitinUbiquitin ThiolesteraseConceptsGLUT4 storage vesiclesTUG cleavageGolgi matrixPlasma membraneGLUT4 glucose transporter translocationMicrotubule-based movementUbiquitin-like proteinGLUT4 glucose transportersStorage vesiclesGlucose transporter translocationAttenuation of insulinKinesin motor proteinsGLUT4 vesiclesSpecialized vesiclesGLUT4 translocationTransporter translocationSplice formsMotor proteinsProtein trapProtein abundanceProteolytic pathwayDiet-induced insulin resistanceEndoproteolytic cleavageGlucose transporterProteolytic processing
2017
Mitochondrial Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation
Lee HY, Lee JS, Alves T, Ladiges W, Rabinovitch PS, Jurczak MJ, Choi CS, Shulman GI, Samuel VT. Mitochondrial Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation. Diabetes 2017, 66: db161334. PMID: 28476930, PMCID: PMC5521865, DOI: 10.2337/db16-1334.Peer-Reviewed Original ResearchConceptsHigh-fat dietMuscle insulin resistanceAcute lipid infusionInsulin resistanceRegular chowLipid infusionMCAT miceInsulin actionLipid-induced insulin resistanceDiet-induced insulin resistanceReactive oxygen speciesHyperinsulinemic-euglycemic clampWild-type miceMuscle fat oxidationIntramuscular lipid accumulationROS productionAcute infusionHFD-fedWT miceImpaired insulinPKCθ activationFat oxidationLipid emulsionMuscle insulinMice
2013
Enhanced Fasting Glucose Turnover in Mice with Disrupted Action of TUG Protein in Skeletal Muscle*
Löffler MG, Birkenfeld AL, Philbrick KM, Belman JP, Habtemichael EN, Booth CJ, Castorena CM, Choi CS, Jornayvaz FR, Gassaway BM, Lee HY, Cartee GD, Philbrick W, Shulman GI, Samuel VT, Bogan JS. Enhanced Fasting Glucose Turnover in Mice with Disrupted Action of TUG Protein in Skeletal Muscle*. Journal Of Biological Chemistry 2013, 288: 20135-20150. PMID: 23744065, PMCID: PMC3711282, DOI: 10.1074/jbc.m113.458075.Peer-Reviewed Original ResearchMeSH Keywords3T3-L1 CellsAdaptor Proteins, Signal TransducingAnimalsBlood GlucoseCarbon DioxideCarrier ProteinsDeoxyglucoseFastingFemaleGlucoseGlucose Transporter Type 4GlycogenGolgi Matrix ProteinsHypoglycemic AgentsImmunoblottingInsulinIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, Inbred StrainsMice, TransgenicMuscle, SkeletalOxygen ConsumptionProtein TransportProteolysisConceptsGLUT4 translocationGLUT4 glucose transportersMuscle-specific transgenic expressionTransgenic miceT-tubule fractionTUG ProteinInsulin signalSystemic glucose homeostasisDiet-induced insulin resistanceHigh-fat diet-induced insulin resistanceEndoproteolytic cleavageTransgenic expressionTransgenic muscleGlucose transporterCell surfaceEnergy metabolismProteolysisTranslocationGLUT4Skeletal muscleGlucose uptakeHyperinsulinemic clamp studiesExpressionMetabolic rateTurnover
2007
n-3 Fatty Acids Preserve Insulin Sensitivity In Vivo in a Peroxisome Proliferator–Activated Receptor-α–Dependent Manner
Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher J, Moore IK, Regittnig W, Munoz DS, Kim JH, Shulman GI. n-3 Fatty Acids Preserve Insulin Sensitivity In Vivo in a Peroxisome Proliferator–Activated Receptor-α–Dependent Manner. Diabetes 2007, 56: 1034-1041. PMID: 17251275, DOI: 10.2337/db06-1206.Peer-Reviewed Original ResearchConceptsPPAR alpha-null miceHepatic insulin resistanceHigh-fat diet-induced hepatic insulin resistanceDiacylglycerol-dependent mannerInsulin resistanceWild-type miceFish oil dietOil dietPEPCK gene expressionNull miceDiet-induced hepatic insulin resistanceInsulin sensitivityPPAR-alpha nullSafflower oilFatty acidsGene expressionIsocaloric high-fat dietHigh-fat diet-induced insulin resistanceDiet-induced insulin resistancePeroxisome proliferator-activated receptorLipid abundanceFish oil replacementFish oilHigh-fat dietInsulin-mediated suppression
2005
Adipocyte-Specific Overexpression of FOXC2 Prevents Diet-Induced Increases in Intramuscular Fatty Acyl CoA and Insulin Resistance
Kim JK, Kim HJ, Park SY, Cederberg A, Westergren R, Nilsson D, Higashimori T, Cho YR, Liu ZX, Dong J, Cline GW, Enerback S, Shulman GI. Adipocyte-Specific Overexpression of FOXC2 Prevents Diet-Induced Increases in Intramuscular Fatty Acyl CoA and Insulin Resistance. Diabetes 2005, 54: 1657-1663. PMID: 15919786, DOI: 10.2337/diabetes.54.6.1657.Peer-Reviewed Original ResearchConceptsWild-type miceInsulin resistanceType 2 diabetesAdipocyte-specific overexpressionHigh-fat feedingTg miceGlucose metabolismTransgenic miceDiet-induced hepatic insulin resistanceChronic high-fat feedingTissue-specific insulin actionWhole-body fat massWhole-body glucose metabolismDiet-induced insulin resistanceIntracellular fat contentDiet-induced obesityHigh-fat dietInsulin-mediated suppressionFatty acyl-CoA levelsHepatic insulin resistanceNovel therapeutic targetHepatic glucose productionAcyl-CoA levelsIntramuscular accumulationGlucose intoleranceHormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart
Park SY, Kim HJ, Wang S, Higashimori T, Dong J, Kim YJ, Cline G, Li H, Prentki M, Shulman GI, Mitchell GA, Kim JK. Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart. AJP Endocrinology And Metabolism 2005, 289: e30-e39. PMID: 15701680, DOI: 10.1152/ajpendo.00251.2004.Peer-Reviewed Original ResearchConceptsHSL-KO miceHormone-sensitive lipaseDiet-induced insulin resistanceHSL-deficient miceHigh-fat feedingInsulin resistanceSkeletal muscleGlucose metabolismInsulin actionTissue-specific insulin actionWhole-body fat massGlucose uptakeDiabetic heart failureDiet-induced obesityNormal chow dietBody fat massGroups of miceHyperinsulinemic-euglycemic clampType 2 diabetesFatty acyl-CoA levelsHepatic insulin actionHepatic insulin sensitivityWild-type miceLiver glucose metabolismCardiac glucose uptake
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