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
2018
Effect of a Controlled-Release Mitochondrial Protonophore (CRMP) on Healthspan and Lifespan in Mice
GOEDEKE L, CAMPOREZ J, NASIRI A, WANG Y, ZHANG X, SHULMAN G. Effect of a Controlled-Release Mitochondrial Protonophore (CRMP) on Healthspan and Lifespan in Mice. Diabetes 2018, 67 DOI: 10.2337/db18-123-lb.Peer-Reviewed Original ResearchControlled-release mitochondrial protonophoreCRMP treatmentHepatic steatosisDiet-induced rodent modelWhole body insulin responsivenessInflammation/fibrosisMale C57BL/6J miceWhole-body energy expenditureHyperinsulinemic-euglycemic clampHigh-fat dietType 2 diabetesGlucose infusion rateMitochondrial protonophorePlasma glucose concentrationWide therapeutic indexStrict dietary regimeSecond-generation compoundsTransaminase levelsFatty liverLiver triglyceridesInsulin resistanceAge-related diseasesC57BL/6J miceHepatic triglyceridesFood intake
2013
Reversal of Hypertriglyceridemia, Fatty Liver Disease, and Insulin Resistance by a Liver-Targeted Mitochondrial Uncoupler
Perry RJ, Kim T, Zhang XM, Lee HY, Pesta D, Popov VB, Zhang D, Rahimi Y, Jurczak MJ, Cline GW, Spiegel DA, Shulman GI. Reversal of Hypertriglyceridemia, Fatty Liver Disease, and Insulin Resistance by a Liver-Targeted Mitochondrial Uncoupler. Cell Metabolism 2013, 18: 740-748. PMID: 24206666, PMCID: PMC4104686, DOI: 10.1016/j.cmet.2013.10.004.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseFatty liver diseaseInsulin resistanceLiver diseaseMetabolic syndromeFatty liverSystemic toxicityWhole-body insulin resistanceMajor predisposing conditionReversal of hypertriglyceridemiaTreatment of hypertriglyceridemiaType 2 diabetesMuscle insulin resistanceWide therapeutic indexPredisposing conditionRat modelProtein kinase C epsilonHypertriglyceridemiaTherapeutic indexFed ratsBeneficial effectsLiverPKCθ activitySyndromeMitochondrial uncoupler