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 ResearchConceptsOverexpression 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
2016
Mitochondrial Protonophores For Treatment of NAFLD/NASH and Type 2 Diabetes
Shulman G. Mitochondrial Protonophores For Treatment of NAFLD/NASH and Type 2 Diabetes. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.257.2.Peer-Reviewed Original ResearchType 2 diabetesInsulin resistanceLipid-induced insulin resistanceNAFLD/NASHSkeletal muscleAdipose tissue inflammationEctopic lipid depositionNon-alcoholic steatohepatitisAmerican Diabetes AssociationEctopic lipid depositsAlcoholic steatohepatitisDiabetes AssociationTissue inflammationRecent studiesLipid depositionType 2Lipid depositsHepatic gluconeogenesisCellular mechanismsMitochondrial protonophoreDiabetesMitochondrial inefficiencyLiverMuscleMolecular triggers