2024
SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts
Goedeke L, Ma Y, Gaspar R, Nasiri A, Lee J, Zhang D, Galsgaard K, Hu X, Zhang J, Guerrera N, Li X, LaMoia T, Hubbard B, Haedersdal S, Wu X, Stack J, Dufour S, Butrico G, Kahn M, Perry R, Cline G, Young L, Shulman G. SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts. Journal Of Clinical Investigation 2024, 134: e176708. PMID: 39680452, PMCID: PMC11645152, DOI: 10.1172/jci176708.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter type 2Heart failureKetone oxidationGas chromatography-mass spectrometryFatty acid oxidationLeft ventricular ejection fractionReduced myocardial oxidative stressVentricular ejection fractionKetone supplementationWeeks of treatmentMyocardial oxidative stressDecreased pyruvate oxidationInduce heart failurePlasma glucose levelsIn vivo effectsSGLT2i treatmentEjection fractionAssociated with improvementsAwake ratsSGLT2 inhibitionCardioprotective benefitsLiquid chromatography-tandem mass spectrometryPlasma ketonesRates of ketonizationChromatography-tandem mass spectrometry
2009
Sensitivity of Lipid Metabolism and Insulin Signaling to Genetic Alterations in Hepatic Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α Expression
Estall JL, Kahn M, Cooper MP, Fisher FM, Wu MK, Laznik D, Qu L, Cohen DE, Shulman GI, Spiegelman BM. Sensitivity of Lipid Metabolism and Insulin Signaling to Genetic Alterations in Hepatic Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α Expression. Diabetes 2009, 58: 1499-1508. PMID: 19366863, PMCID: PMC2699879, DOI: 10.2337/db08-1571.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBlood GlucoseBody CompositionCell Culture TechniquesCrosses, GeneticFatty LiverFemaleGene Expression RegulationHepatocytesHomeostasisInsulinInsulin ResistanceIntegrasesKetonesLipidsLiverMiceMice, TransgenicPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaRNA, Small InterferingTrans-ActivatorsTranscription FactorsTriglyceridesConceptsPGC-1alpha levelsCre/lox systemExpression of genesKey metabolic enzymesKey metabolic pathwaysPGC-1alpha activityPGC-1alpha expressionPeroxisome proliferator-activated receptor gamma coactivatorReceptor γ coactivatorLipid metabolismProliferator-activated receptor gamma coactivatorComplete genetic ablationTranscriptional coactivatorNutrient deprivationReceptor gamma coactivatorPGC-1alphaFatty acid oxidationOxidative phosphorylationMetabolic enzymesLox systemCoactivatorLipid homeostasisMetabolic pathwaysGenetic ablationGenetic alterations