2023
Time-restricted feeding combined with resistance exercise prevents obesity and improves lipid metabolism in the liver of mice fed a high-fat diet
Damasceno de Lima R, Fudoli Lins Vieira R, Rosetto Muñoz V, Chaix A, Azevedo Macedo A, Calheiros Antunes G, Felonato M, Rosseto Braga R, Castelo Branco Ramos Nakandakari S, Calais Gaspar R, Ramos da Silva A, Esper Cintra D, Pereira de Moura L, Mekary R, Rochete Ropelle E, Pauli J. Time-restricted feeding combined with resistance exercise prevents obesity and improves lipid metabolism in the liver of mice fed a high-fat diet. AJP Endocrinology And Metabolism 2023, 325: e513-e528. PMID: 37755454, DOI: 10.1152/ajpendo.00129.2023.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseResistance exercise trainingTime-restricted feedingFatty liver diseaseHigh-fat dietLiver diseaseExercise trainingWeight gainGlycemic homeostasisMetabolic disordersEffects of TRFCommon liver diseaseDiet-induced obesityMajor risk factorEnergy expenditureFatty acid oxidation genesLiver of miceAccumulation of fatBody weight gainRespiratory exchange rateAccumulation of lipidsLower mRNA expressionRT groupPrevents obesityRisk factorsMAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis.
Park J, Hall C, Hubbard B, LaMoia T, Gaspar R, Nasiri A, Li F, Zhang H, Kim J, Haeusler R, Accili D, Shulman G, Yu H, Choi E. MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis. Diabetes 2023, 72: 1781-1794. PMID: 37725942, PMCID: PMC10658066, DOI: 10.2337/db23-0314.Peer-Reviewed Original ResearchConceptsIR endocytosisInsulin receptor endocytosisCell division regulatorsInsulin receptorProlongs insulin actionReceptor endocytosisTranscriptomic profilesInsulin stimulationEndocytosisMetabolic homeostasisCell surfaceGenetic ablationMetabolic functionsInsulin actionP31cometMad2BubR1DisruptionSignalingRegulatorHomeostasisAdipose tissueInteractionHepatic fat accumulationMetabolismDichloroacetate 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 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 ResearchConceptsWhole-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 functionShort-term flaxseed oil, rich in omega 3, protects mice against metabolic damage caused by high-fat diet, but not inflammation
Nakandakari S, Gaspar R, Kuga G, Ramos C, Vieira R, Rios T, Muñoz V, Sant'ana M, Simabuco F, da Silva A, Moura L, Ropelle E, Pauli J, Cintra D. Short-term flaxseed oil, rich in omega 3, protects mice against metabolic damage caused by high-fat diet, but not inflammation. The Journal Of Nutritional Biochemistry 2023, 114: 109270. PMID: 36706930, DOI: 10.1016/j.jnutbio.2023.109270.Peer-Reviewed Original ResearchConceptsControl groupFood intakeAdipose tissueLong-term high-fat diet feedingHigh-fat diet feedingFlaxseed oilHigh-fat dietMesenteric adipose tissueFatty acid incorporationNeuronal signaling pathwaysInflammatory markersHF dietInflammatory effectsDiet feedingEarly inflammationHF groupLipid profileTNFα proteinProtective effectTriggers inflammationMetabolic disordersGlucose homeostasisBody weightInflammationHF consumptionInhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis
Luukkonen P, Sakuma I, Gaspar R, Mooring M, Nasiri A, Kahn M, Zhang X, Zhang D, Sammalkorpi H, Penttilä A, Orho-Melander M, Arola J, Juuti A, Zhang X, Yimlamai D, Yki-Järvinen H, Petersen K, Shulman G. Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2217543120. PMID: 36669104, PMCID: PMC9942818, DOI: 10.1073/pnas.2217543120.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseLiver fibrosisLiver diseaseCommon chronic liver diseaseChronic liver diseaseFatty liver diseaseRisk of fibrosisDistinct mouse modelsPyrimidine catabolismNonalcoholic steatohepatitisMouse modelTherapeutic targetFibrosisDihydropyrimidine dehydrogenaseHuman liverA variantCommon variantsMetabolomics approachDiseaseMiceInhibitionCatabolismKnockdownSteatohepatitisGimeracil
2022
Aging reduces ABHD5 protein content in the adipose tissue of mice: The reversal effect of exercise
Brícola R, Cordeiro A, Crisol B, Braga R, de Melo D, Rocha M, Gaspar R, Nakandakari S, Silva V, Anaruma C, Katashima C, Canciglieri R, Munõz V, Pavan I, Pinto A, Simabuco F, da Silva A, Moura L, Pauli J, Cintra D, Ropelle E. Aging reduces ABHD5 protein content in the adipose tissue of mice: The reversal effect of exercise. Cell Biochemistry And Function 2022, 41: 128-137. PMID: 36515301, DOI: 10.1002/cbf.3770.Peer-Reviewed Original ResearchConceptsAged miceAdipose tissueControl of lipolysisHigh-intensity interval trainingSubcutaneous white adipose tissueExperimental mouse modelAdipose tissue metabolismWhite adipose tissueMessenger RNA levelsInterval trainingMouse modelTissue metabolismLipolytic pathwayMiceRNA levelsProtein levelsScWATTranscriptomic analyzesReversal effectTissueExerciseSignificant hallmarkLipolysisABHD5Lipolytic activityDistinct 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 findingsShort-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents
Muñoz V, Gaspar R, Mancini M, de Lima R, Vieira R, Crisol B, Antunes G, Trombeta J, Bonfante I, Simabuco F, da Silva A, Cavaglieri C, Ropelle E, Cintra D, Pauli J. Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents. Journal Of Endocrinological Investigation 2022, 46: 815-827. PMID: 36318449, DOI: 10.1007/s40618-022-01947-8.Peer-Reviewed Original ResearchConceptsInsulin sensitivityHepatic metabolismPhysical exerciseInsulin resistanceAerobic exerciseMetabolic healthAged rodentsShort-term aerobic exerciseAge-related insulin resistanceShort-term exercise trainingSignificant metabolic impairmentType 2 diabetesHepatic fat accumulationWhole-body glucoseDevelopment/progressionHepatic fat metabolismExercise trainingGlucose toleranceInsulin secretionFat accumulationHigh prevalenceHyperinsulinemic ratsMetabolic impairmentElderly populationGlucose homeostasis
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 proteinTime‐restricted feeding combined with aerobic exercise training can prevent weight gain and improve metabolic disorders in mice fed a high‐fat diet
Vieira R, Muñoz V, Junqueira R, de Oliveira F, Gaspar R, Nakandakari S, de Oliveira Costa S, Torsoni M, da Silva A, Cintra D, de Moura L, Ropelle E, Zaghloul I, Mekary R, Pauli J. Time‐restricted feeding combined with aerobic exercise training can prevent weight gain and improve metabolic disorders in mice fed a high‐fat diet. The Journal Of Physiology 2021, 600: 797-813. PMID: 33450053, DOI: 10.1113/jp280820.Peer-Reviewed Original ResearchConceptsTime-restricted feedingHigh-fat dietAerobic exercise trainingMale Swiss miceHigh-fat diet feedingFatty acid oxidationSwiss miceExercise trainingMetabolic disordersDiet feedingLiver metabolismAE trainingAcid oxidationLower serum triglyceridesHepatic lipid accumulationHepatic lipid contentImproved hepatic metabolismLipogenic gene expressionSerum triglyceridesAdiposity gainBody adiposityGlycaemic homeostasisInsulin sensitivityHepatic metabolismGlucose metabolism
2020
Acute physical exercise increases PI3K‐p110α protein content in the hypothalamus of obese mice
Gaspar R, Nakandakari S, Muñoz V, Vieira R, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Acute physical exercise increases PI3K‐p110α protein content in the hypothalamus of obese mice. Journal Of Anatomy 2020, 238: 743-750. PMID: 33094520, PMCID: PMC7855078, DOI: 10.1111/joa.13342.Peer-Reviewed Original ResearchConceptsObese miceAcute exerciseFood intakePhysical exerciseCumulative food intakeBlood-brain barrierAcute physical exerciseEnergy homeostasis controlSuppressor of cytokineMain adipokinesHypothalamic nucleiPeripheral organsObese animalsLeptin signalingHypothalamusInsulin actionCentral signalingLeptinProtein levelsActivation of phosphoinositideMiceInsulin pathwayExerciseIntakeHomeostasis controlWhen fasting results in metabolic damage: a matter of sex
Muñoz V, Vieira R, Gaspar R. When fasting results in metabolic damage: a matter of sex. The Journal Of Physiology 2020, 598: 3067-3069. PMID: 32406089, DOI: 10.1113/jp279873.Peer-Reviewed Original Research
2019
Tlr4 participates in the responses of markers of apoptosis, inflammation, and ER stress to different acute exercise intensities in mice hearts
de Vicente L, Pinto A, Muñoz V, Rovina R, da Rocha A, Gaspar R, da Silva L, Simabuco F, Frantz F, Pauli J, de Moura L, Cintra D, Ropelle E, da Silva A. Tlr4 participates in the responses of markers of apoptosis, inflammation, and ER stress to different acute exercise intensities in mice hearts. Life Sciences 2019, 240: 117107. PMID: 31785241, DOI: 10.1016/j.lfs.2019.117107.Peer-Reviewed Original ResearchConceptsAcute exercise intensityAcute physical exerciseLeft ventricleTLR4 deletionIL-17Serum levelsTNF-alphaPhysical exerciseExercise intensityER stressToll-like receptor 4Heart mRNA levelsSame exercise conditionTLR4 KO miceRole of TLR4Myocardium of miceExpression of inflammationResponse of markersEndoplasmic reticulum stressKO miceReceptor 4CK-MBImmune responseInflammationER stress genesNAD+ 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 ResearchConceptsNR supplementationSkeletal muscleMitochondrial markersMitochondrial proteinsTranscriptomic analysisRate-limiting enzymePhysiological assaysMitochondrial metabolismMitochondrial biogenesisMitochondrial oxidative capacityBXD miceIsogenic strainsDifferent phenotypesProtein contentMolecular assaysAerobic performanceOxidative capacityMuscle metabolismMetabolismBiogenesisMTCO1AssaysLarge panelBiosynthesisGenesAcute physical exercise increases APPL1/PI3K signaling in the hypothalamus of lean mice
Gaspar R, Muñoz V, Kuga G, Nakandakari S, Crisol B, Lenhare L, Breda L, Botezelli J, Sant'Ana M, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Acute physical exercise increases APPL1/PI3K signaling in the hypothalamus of lean mice. European Journal Of Neuroscience 2019, 50: 3181-3190. PMID: 31206806, DOI: 10.1111/ejn.14490.Peer-Reviewed Original ResearchConceptsLean miceExercise sessionsPhysical exerciseAcute exercise sessionAcute physical exercisePhysical exercise sessionPI3K p110PI3K mRNAAdiponectin pathwayArcuate nucleusSwiss miceHypothalamusAdiponectinEnergy homeostasisMiceMRNA levelsPI3KFood consumptionLeucine zipper motif 1BXD miceExerciseK mRNAPresent studyPositive correlationKey proteinsShort-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet
Minuzzi L, Kuga G, Breda L, Gaspar R, Muñoz V, Pereira R, Botezelli J, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Short-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet. Experimental And Clinical Endocrinology & Diabetes 2019, 128: 30-37. PMID: 30991419, DOI: 10.1055/a-0885-9872.Peer-Reviewed Original ResearchConceptsLong-term high-fat dietShort-term resistance trainingHigh-fat dietResistance trainingInsulin sensitivityHigh calorie intakeLiver of miceAdiponectin pathwayChow dietMice fedInsulin resistanceGlycemic homeostasisSwiss miceAdiponectin receptorsPhysical activityPhysical exerciseInsulin actionHepatic tissueMiceLiverDietAdiponectinInadequate levelsAdverse consequencesCritical regulatorShort-term high-fat diet modulates several inflammatory, ER stress, and apoptosis markers in the hippocampus of young mice
Nakandakari S, Muñoz V, Kuga G, Gaspar R, Sant'Ana M, Pavan I, da Silva L, Morelli A, Simabuco F, da Silva A, de Moura L, Ropelle E, Cintra D, Pauli J. Short-term high-fat diet modulates several inflammatory, ER stress, and apoptosis markers in the hippocampus of young mice. Brain Behavior And Immunity 2019, 79: 284-293. PMID: 30797044, DOI: 10.1016/j.bbi.2019.02.016.Peer-Reviewed Original ResearchConceptsHigh-fat dietYoung miceShort-term HFD feedingMice fed high-fat dietFed high-fat dietHippocampus of miceER stressDisease developmentShort-term consumptionAlzheimer's disease developmentPotential molecular mechanismsHOMA-IRHFD feedingAD markersMicroglial cellsAD pathogenesisRisk factorsInflammatory signalsDiet modulatesΒ-amyloidCleaved caspase3HippocampusApoptosis markersHigh expressionMice
2018
Unsaturated fatty acids from flaxseed oil and exercise modulate GPR120 but not GPR40 in the liver of obese mice: a new anti-inflammatory approach
Gaspar R, Veiga C, Bessi M, Dátilo M, Sant'Ana M, Rodrigues P, de Moura L, da Silva A, Santos G, Catharino R, Ropelle E, Pauli J, Cintra D. Unsaturated fatty acids from flaxseed oil and exercise modulate GPR120 but not GPR40 in the liver of obese mice: a new anti-inflammatory approach. The Journal Of Nutritional Biochemistry 2018, 66: 52-62. PMID: 30771734, DOI: 10.1016/j.jnutbio.2018.12.003.Peer-Reviewed Original ResearchConceptsHigh-fat dietPhysical exerciseObese miceNew anti-inflammatory approachesFlaxseed oilAnti-inflammatory approachesAnti-inflammatory propertiesChronic physical exerciseImpact of exerciseType 2 diabetesInflammatory markersInflammatory responseExercise performanceHepatic metabolismGPR120Fat depotsSources of ω3GPR40ObesityLiverΒ-arrestinMiceRelated cascadesExerciseInsulin