2022
Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo
Codella R, Alves TC, Befroy DE, Choi CS, Luzi L, Rothman DL, Kibbey RG, Shulman GI. Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo. FEBS Letters 2022, 597: 309-319. PMID: 36114012, DOI: 10.1002/1873-3468.14494.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsIon ChannelsMiceMitochondriaMitochondria, MuscleMitochondrial ProteinsMuscle, SkeletalProtonsUncoupling Protein 3ConceptsOverexpression of UCP3ATP synthesisMitochondrial oxidationMitochondrial transmembrane proteinInner mitochondrial membraneSkeletal muscleMitochondrial oxidative phosphorylationMitochondrial oxidative metabolismMuscle-specific overexpressionMouse skeletal muscleTransmembrane proteinMitochondrial membraneProton leakPrecise functionOxidative phosphorylationMitochondrial efficiencyUCP3 expressionMitochondrial inefficiencyOverexpressionProtein 3UCP3Oxidative metabolismVivoMagnetic resonance spectroscopyPhosphorylation
2021
Therapeutic potential of mitochondrial uncouplers for the treatment of metabolic associated fatty liver disease and NASH
Goedeke L, Shulman GI. Therapeutic potential of mitochondrial uncouplers for the treatment of metabolic associated fatty liver disease and NASH. Molecular Metabolism 2021, 46: 101178. PMID: 33545391, PMCID: PMC8085597, DOI: 10.1016/j.molmet.2021.101178.Peer-Reviewed Original ResearchConceptsFatty liver diseaseLiver diseaseSmall molecule mitochondrial uncouplersTherapeutic potentialMitochondrial uncouplerNon-human primate studiesType 2 diabetesWide therapeutic indexSystemic toxicity concernsTreatment of MetabolicCell-specific effectsInsulin resistanceTherapeutic indexMetabolic diseasesNonalcoholic hepatosteatosisSustained increaseToxicity concernsPrimate studiesDiseaseTherapeutic developmentMitochondrial inefficiencyNutrient oxidationATP productionTreatmentTissue
2004
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes. New England Journal Of Medicine 2004, 350: 664-671. PMID: 14960743, PMCID: PMC2995502, DOI: 10.1056/nejmoa031314.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdipose TissueBlood GlucoseDiabetes Mellitus, Type 2Fatty AcidsFemaleGlucoseGlucose Clamp TechniqueGlucose Tolerance TestGlycerolHumansInsulinInsulin ResistanceLipolysisMagnetic Resonance SpectroscopyMaleMitochondriaMuscle, SkeletalOxidative PhosphorylationTriglyceridesConceptsInsulin-resistant offspringType 2 diabetesIntramyocellular lipid contentInsulin-sensitive control subjectsMagnetic resonance spectroscopy studyInsulin resistanceControl subjectsProton magnetic resonance spectroscopy studyHyperinsulinemic-euglycemic clamp studiesTumor necrosis factor alphaImpaired mitochondrial activityIntrahepatic triglyceride contentDevelopment of diabetesChildren of patientsInsulin-resistant subjectsNecrosis factor alphaSensitivity of liverInsulin-stimulated ratesFatty acid metabolismMitochondrial oxidative phosphorylation activityInterleukin-6Intramyocellular lipidsPlasma concentrationsFactor alphaClamp studies
2001
Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle
Lebon V, Dufour S, Petersen K, Ren J, Jucker B, Slezak L, Cline G, Rothman D, Shulman G. Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle. Journal Of Clinical Investigation 2001, 108: 733-737. PMID: 11544279, PMCID: PMC209375, DOI: 10.1172/jci11775.Peer-Reviewed Original ResearchConceptsSkeletal muscleUncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, β Cell Dysfunction, and Type 2 Diabetes
Zhang C, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, Hagen T, Vidal-Puig A, Boss O, Kim Y, Zheng X, Wheeler M, Shulman G, Chan C, Lowell B. Uncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, β Cell Dysfunction, and Type 2 Diabetes. Cell 2001, 105: 745-755. PMID: 11440717, DOI: 10.1016/s0092-8674(01)00378-6.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBlood GlucoseBody WeightDiabetes MellitusDiabetes Mellitus, Type 2Disease Models, AnimalGene TargetingHomeostasisHumansHyperglycemiaInsulinInsulin SecretionIon ChannelsIslets of LangerhansMaleMembrane Transport ProteinsMiceMice, KnockoutMice, ObeseMitochondrial ProteinsModels, BiologicalObesityProteinsRNA, MessengerThermogenesisUncoupling AgentsUncoupling Protein 2ConceptsOb/ob miceInsulin secretionOb miceCell dysfunctionFirst-phase insulin secretionIslet ATP levelsGlucose-stimulated insulin secretionLevel of glycemiaSerum insulin levelsBeta-cell dysfunctionType 2 diabetesObesity-induced diabetesΒ-cell dysfunctionBeta-cell glucose sensingProtein 2UCP2-deficient miceInsulin levelsPathophysiologic significanceBeta cellsType 2SecretionMiceObesityATP levelsDiabetes
2000
13C/31P NMR Assessment of Mitochondrial Energy Coupling in Skeletal Muscle of Awake Fed and Fasted Rats RELATIONSHIP WITH UNCOUPLING PROTEIN 3 EXPRESSION*
Jucker B, Ren J, Dufour S, Cao X, Previs S, Cadman K, Shulman G. 13C/31P NMR Assessment of Mitochondrial Energy Coupling in Skeletal Muscle of Awake Fed and Fasted Rats RELATIONSHIP WITH UNCOUPLING PROTEIN 3 EXPRESSION*. Journal Of Biological Chemistry 2000, 275: 39279-39286. PMID: 10995775, DOI: 10.1074/jbc.m007760200.Peer-Reviewed Original ResearchAdenosine TriphosphateAlbuminsAnimalsBlotting, NorthernBlotting, WesternCarnitine O-PalmitoyltransferaseCarrier ProteinsEnzyme InhibitorsEpoxy CompoundsFatty AcidsFood DeprivationGlutamic AcidIon ChannelsKineticsMagnetic Resonance SpectroscopyMitochondriaMitochondrial ProteinsModels, BiologicalModels, ChemicalMuscle, SkeletalOxygenPalmitatesRatsRats, Sprague-DawleyRNA, MessengerTime FactorsTricarboxylic AcidsUncoupling Protein 3Assessment of mitochondrial energy coupling in vivo by 13C/31P NMR
Jucker B, Dufour S, Ren J, Cao X, Previs S, Underhill B, Cadman K, Shulman G. Assessment of mitochondrial energy coupling in vivo by 13C/31P NMR. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 6880-6884. PMID: 10823916, PMCID: PMC18769, DOI: 10.1073/pnas.120131997.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCitric Acid CycleEnergy MetabolismMagnetic Resonance SpectroscopyMitochondriaObesityOxidation-ReductionRatsRats, Sprague-DawleyConceptsUCP3 mRNAPersistent Changes in Myocardial Glucose Metabolism In Vivo During Reperfusion of a Limited-Duration Coronary Occlusion
McNulty P, Jagasia D, Cline G, Ng C, Whiting J, Garg P, Shulman G, Soufer R. Persistent Changes in Myocardial Glucose Metabolism In Vivo During Reperfusion of a Limited-Duration Coronary Occlusion. Circulation 2000, 101: 917-922. PMID: 10694532, DOI: 10.1161/01.cir.101.8.917.Peer-Reviewed Original ResearchConceptsCoronary occlusionGlucose metabolismPostischemic stunningAnterolateral left ventricleHeart glucose metabolismCoronary artery occlusionRegional glucose metabolismMyocardial glucose metabolismRegional myocardial ischemiaRegional mechanical functionRapid reperfusionReversible coronary occlusionArtery occlusionMyocardial ischemiaIntact ratsPreferential shuntingBlood flowReperfusionTracer uptakeLeft ventricleGlycogen depletionMetabolic signaturesOcclusionPersistent changesSustained changes