2023
Tissue-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 expressionEffects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4+/− mice
Muñoz V, Botezelli J, Gaspar R, da Rocha A, Vieira R, Crisol B, Braga R, Severino M, Nakandakari S, Antunes G, Brunetto S, Ramos C, Velloso L, Simabuco F, de Moura L, da Silva A, Ropelle E, Cintra D, Pauli J. Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4+/− mice. Cellular And Molecular Life Sciences 2023, 80: 122. PMID: 37052684, PMCID: PMC11072257, DOI: 10.1007/s00018-023-04771-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 2GlucoseGlucose Transporter Type 4HyperglycemiaInsulin ResistanceMiceMuscle, SkeletalConceptsWhole-body glucose homeostasisSkeletal muscle glucose uptakeMuscle glucose uptakeMitochondrial adaptationsMitochondrial activityPost-translational mechanismsSkeletal muscleGlucose uptakeC2C12 cell lineInsulin resistanceStrength exercisesGlucose homeostasisMouse modelPhysical exerciseProtein response markersShort-term physical activityMolecular regulationTranscriptomic modulationRNA sequencingImpact of hyperglycemiaC2C12 cellsStrength exercise trainingType 2 diabetesStrength training protocolsMitochondrial function
2022
Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice
Gaspar R, Lyu K, Hubbard B, Leitner B, Luukkonen P, Hirabara S, Sakuma I, Nasiri A, Zhang D, Kahn M, Cline G, Pauli J, Perry R, Petersen K, Shulman G. Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice. Diabetologia 2022, 66: 567-578. PMID: 36456864, PMCID: PMC11194860, DOI: 10.1007/s00125-022-05838-8.Peer-Reviewed Original ResearchConceptsProtein kinase CsSubcellular compartmentsDistinct subcellular localisationMuscle insulin sensitivityMultiple subcellular compartmentsInsulin receptor kinaseNovel protein kinase CsActivation of PKCεSubcellular localisationPKCθ translocationReceptor kinasePlasma membraneSubcellular distributionTriacylglycerol contentCrucial pathwaysIntramuscular triacylglycerol contentRC miceDiacylglycerolConclusions/interpretationThese resultsPKCεPM compartmentPhosphorylationMuscle triacylglycerol contentSkeletal muscleRecent findings
2021
Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice
Muñoz V, Gaspar R, Severino M, Macêdo A, Simabuco F, Ropelle E, Cintra D, da Silva A, Kim Y, Pauli J. Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice. Frontiers In Immunology 2021, 12: 702025. PMID: 34234788, PMCID: PMC8256841, DOI: 10.3389/fimmu.2021.702025.Peer-Reviewed Original ResearchConceptsSkeletal muscleInsulin receptor substrate-1Protein tyrosine phosphatase 1BSkeletal muscle glucose uptakeGlucose uptakeProtein kinase BReceptor substrate-1Muscle glucose uptakePhosphatase 1BRho kinase isoformsSubstrate-1Kinase BMolecular mechanismsSystemic glucose homeostasisTensin homologC2C12 myotubesAkt phosphorylationHigher phosphorylationMolecular analysisMuscle insulinInhibitory regulatorPotential targetRhoA-ROCK2PhosphorylationROCK2 protein
2020
Effects of short-term physical training on the interleukin-15 signalling pathway and glucose tolerance in aged rats
Minuzzi L, da Conceição L, Muñoz V, Vieira R, Gaspar R, da Silva A, Cintra D, Pereira de Moura L, Ropelle E, Teixeira A, Pauli J. Effects of short-term physical training on the interleukin-15 signalling pathway and glucose tolerance in aged rats. Cytokine 2020, 137: 155306. PMID: 33010727, DOI: 10.1016/j.cyto.2020.155306.Peer-Reviewed Original ResearchConceptsAerobic physical trainingInsulin sensitivityIL-15Physical trainingGlucose toleranceInterleukin-15Elderly ratsWhole-body insulin sensitivityShort-term physical trainingSkeletal muscleLast exercise sessionExercise training protocolMesenteric fat massPhysical exercise trainingPhysical exercise protocolSkeletal muscle alterationsFourteen Wistar ratsExpression of HIF1αExercise trainingExercise protocolExercise sessionsMuscle alterationsFat massWistar ratsSupraphysiological levelsPhysical exercise increases ROCK activity in the skeletal muscle of middle-aged rats
Muñoz V, Gaspar R, Esteca M, Baptista I, Vieira R, da Silva A, de Moura L, Cintra D, Ropelle E, Pauli J. Physical exercise increases ROCK activity in the skeletal muscle of middle-aged rats. Mechanisms Of Ageing And Development 2020, 186: 111213. PMID: 32032622, DOI: 10.1016/j.mad.2020.111213.Peer-Reviewed Original ResearchConceptsMiddle-aged ratsSoleus musclePhysical exerciseGlucose homeostasisAge-related metabolic disordersSkeletal muscle glucose uptakeSkeletal muscleImpaired glucose homeostasisType 2 diabetesMuscle glucose uptakeInsulin receptor substrate-1 phosphorylationWhole-body glucose homeostasisROCK activitySkeletal muscle fiber typesMuscle fiber typesInsulin resistanceSedentary ratsHigh insulinDifferent skeletal muscle fiber typesMetabolic disordersMetabolism-related genesPharmacological inhibitionRatsGlucose uptakeMuscle
2019
Rho-kinase activity is upregulated in the skeletal muscle of aged exercised rats
Muñoz V, Gaspar R, Minuzzi L, Dos Santos Canciglieri R, da Silva A, de Moura L, Cintra D, Ropelle E, Pauli J. Rho-kinase activity is upregulated in the skeletal muscle of aged exercised rats. Experimental Gerontology 2019, 128: 110746. PMID: 31629802, DOI: 10.1016/j.exger.2019.110746.Peer-Reviewed Original ResearchNAD+ precursor increases aerobic performance in mice
Crisol B, Veiga C, Braga R, Lenhare L, Baptista I, Gaspar R, Muñoz V, Cordeiro A, da Silva A, Cintra D, Moura L, Pauli J, Ropelle E. NAD+ precursor increases aerobic performance in mice. European Journal Of Nutrition 2019, 59: 2427-2437. PMID: 31494696, DOI: 10.1007/s00394-019-02089-z.Peer-Reviewed Original ResearchMeSH KeywordsAerobiosisAnimalsCell RespirationMaleMiceMice, Inbred C57BLMitochondriaMuscle, SkeletalNADNiacinamidePyridinium CompoundsConceptsNR supplementationSkeletal muscleMitochondrial markersMitochondrial proteinsTranscriptomic analysisRate-limiting enzymePhysiological assaysMitochondrial metabolismMitochondrial biogenesisMitochondrial oxidative capacityBXD miceIsogenic strainsDifferent phenotypesProtein contentMolecular assaysAerobic performanceOxidative capacityMuscle metabolismMetabolismBiogenesisMTCO1AssaysLarge panelBiosynthesisGenesExhaustive acute exercise-induced ER stress is attenuated in IL-6-knockout mice
Pinto A, da Rocha A, Kohama E, Gaspar R, Simabuco F, Frantz F, de Moura L, Pauli J, Cintra D, Ropelle E, de Freitas E, da Silva A. Exhaustive acute exercise-induced ER stress is attenuated in IL-6-knockout mice. Journal Of Endocrinology 2019, 240: 181-193. PMID: 30400033, DOI: 10.1530/joe-18-0404.Peer-Reviewed Original ResearchConceptsIL-6 knockout miceExtensor digitorium longusPhysical exercise protocolAcute exercise protocolER stress proteinsExercise protocolIL-6WT groupIL-6 KO groupSerum levelsKO groupExercise-induced IL-6IL-6 concentrationsWild-type miceIntense physical exerciseER stressEndoplasmic reticulum stressStress proteinsIL-10Interleukin-6Knockout micePhysical exerciseSoleusHomeostatic functionsMice
2018
The Effects of Aging on Rho-Kinase and Insulin Signaling in Skeletal Muscle and White Adipose Tissue of Rats
Muñoz V, Gaspar R, Kuga G, Pavan I, Simabuco F, da Silva A, de Moura L, Cintra D, Ropelle E, Pauli J. The Effects of Aging on Rho-Kinase and Insulin Signaling in Skeletal Muscle and White Adipose Tissue of Rats. The Journals Of Gerontology Series A 2018, 75: 432-436. PMID: 30596894, DOI: 10.1093/gerona/gly293.Peer-Reviewed Original ResearchThe reversal effect of physical exercise on aging-related increases in APPL2 content in skeletal muscle
Canciglieri P, Kuga G, Muñoz V, Gaspar R, da Rocha A, Breda L, Anaruma C, Minuzzi L, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. The reversal effect of physical exercise on aging-related increases in APPL2 content in skeletal muscle. Life Sciences 2018, 210: 209-213. PMID: 30189216, DOI: 10.1016/j.lfs.2018.09.006.Peer-Reviewed Original ResearchConceptsExercise training protocolFischer 344 ratsPhysical exerciseOld ratsShort-term exercise trainingNon-pharmacological therapeutic interventionsSkeletal muscleTraining protocolPossible therapeutic effectsAdiponectin receptor 1Old Fischer 344 ratsAge-related increaseGlucose intoleranceExercise trainingGlucose toleranceAdiponectin signalingTherapeutic effectTherapeutic interventionsAge-related deficitsReceptor 1RatsAkt phosphorylationReversal effectExerciseIsoform 1Exercise increases Rho‐kinase activity and insulin signaling in skeletal muscle
Muñoz V, Gaspar R, Kuga G, da Rocha A, Crisol B, Botezelli J, Baptista I, Mekary R, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Exercise increases Rho‐kinase activity and insulin signaling in skeletal muscle. Journal Of Cellular Physiology 2018, 233: 4791-4800. PMID: 29219181, DOI: 10.1002/jcp.26278.Peer-Reviewed Original Research
2017
The role of physical exercise on Sestrin1 and 2 accumulations in the skeletal muscle of mice
Crisol B, Lenhare L, Gaspar R, Gaspar R, Muñoz V, da Silva A, Cintra D, de Moura L, Pauli J, Ropelle E. The role of physical exercise on Sestrin1 and 2 accumulations in the skeletal muscle of mice. Life Sciences 2017, 194: 98-103. PMID: 29273527, DOI: 10.1016/j.lfs.2017.12.023.Peer-Reviewed Original ResearchConceptsStress-related proteinsThreonine phosphorylationBXD miceSkeletal muscleSesn2 mRNATranscriptomic analysisProtein contentBioinformatics analysisIsogenic strainsSestrin 1SestrinsSESN1Phenotypic patternsSestrin1Sestrin2 expressionPhosphorylationMRNA levelsWestern blotProteinNew insightsExperimental approachBasal levelsLarge panelAccumulationMice