2023
Dichloroacetate as a novel pharmaceutical treatment for cancer-related fatigue in melanoma
Zhang X, Lee W, Leitner B, Zhu W, Fosam A, Li Z, Gaspar R, Halberstam A, Robles B, Rabinowitz J, Perry R. Dichloroacetate as a novel pharmaceutical treatment for cancer-related fatigue in melanoma. AJP Endocrinology And Metabolism 2023, 325: e363-e375. PMID: 37646579, PMCID: PMC10642987, DOI: 10.1152/ajpendo.00105.2023.Peer-Reviewed Original ResearchConceptsCancer-related fatigueNovel pharmaceutical treatmentsPhysical functionPharmaceutical treatmentTumor growthCancer treatmentStandard cancer treatmentTumor-bearing miceLate-stage tumorsEffective pharmaceutical treatmentMurine cancer modelsNew metabolic targetsMultiple cancer typesAdjuvant therapyCommon complicationPatients' qualitySymptom managementClinical trialsMurine modelPotential therapyPharmaceutical therapySmall molecule inhibitorsCancer modelDCA treatmentLactate concentrationTissue-specific reprogramming of glutamine metabolism maintains tolerance to sepsis
Leitner B, Lee W, Zhu W, Zhang X, Gaspar R, Li Z, Rabinowitz J, Perry R. Tissue-specific reprogramming of glutamine metabolism maintains tolerance to sepsis. PLOS ONE 2023, 18: e0286525. PMID: 37410734, PMCID: PMC10325078, DOI: 10.1371/journal.pone.0286525.Peer-Reviewed Original ResearchConceptsTCA cycle anaplerosisGlobal mitochondrial dysfunctionAromatic amino acid transportAmino acid transportTissue-specific metabolic responsesMurine polymicrobial sepsis modelMetabolic signaturesAntioxidant metabolismGlutathione biosynthesisMitochondrial metabolismTCA cycleGreat therapeutic interestEnergetic demandsPolymicrobial sepsis modelAntioxidant synthesisUnique metabolic signatureGlutamine metabolismMitochondrial dysfunctionAcid transportMuscle transcriptomicsGlutathione cyclingATP ratioIsotope tracingCritical illnessReduced expression
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