2023
Inhibition 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 activity
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 control
2019
Acute 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 expressionMiceExhaustive 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
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 cascadesExerciseInsulinAcute physical exercise increases leptin‐induced hypothalamic extracellular signal‐regulated kinase1/2 phosphorylation and thermogenesis of obese mice
Gaspar R, Muñoz V, Kuga G, Nakandakari S, Minuzzi L, Botezelli J, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Acute physical exercise increases leptin‐induced hypothalamic extracellular signal‐regulated kinase1/2 phosphorylation and thermogenesis of obese mice. Journal Of Cellular Biochemistry 2018, 120: 697-704. PMID: 30206970, DOI: 10.1002/jcb.27426.Peer-Reviewed Original ResearchConceptsAcute physical exerciseBrown adipose tissueObese micePhysical exerciseEnergy expenditureERK1/2 phosphorylationTreatment of obesityExtracellular signal-regulated kinase1/2 (ERK1/2) phosphorylationProtein 1 (UCP1) contentExtracellular signal-regulated kinase 1/2Signal-regulated kinase 1/2Sympathetic signalsSpontaneous activityAdipose tissueP-ERK1/2Main interventionThermoregulatory effectsMiceKey mediatorThermogenesisOxygen uptakeMolecular changesKinase 1/2ObeseObesityAcute physical exercise increases the adaptor protein APPL1 in the hypothalamus of obese mice
Gaspar R, Muñoz V, Formigari G, Kuga G, Nakandakari S, Botezelli J, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Acute physical exercise increases the adaptor protein APPL1 in the hypothalamus of obese mice. Cytokine 2018, 110: 87-93. PMID: 29705396, DOI: 10.1016/j.cyto.2018.04.013.Peer-Reviewed Original ResearchConceptsAcute physical exerciseObese micePhysical exerciseFood intakeArcuate proopiomelanocortin neuronsSerum adiponectin levelsProtein-3 levelsEffects of leptinCentral nervous systemRole of APPL1Proopiomelanocortin neuronsAdiponectin levelsAcute exerciseNervous systemHypothalamusPathophysiological processesAdiponectinAdaptor protein APPL1MiceProtein kinase BLeucine zipper motif 1Kinase BExerciseIntakeProtein contentExercise decreases CLK2 in the liver of obese mice and prevents hepatic fat accumulation
Muñoz V, Gaspar R, Kuga G, Nakandakari S, Baptista I, Mekary R, da Silva A, de Moura L, Ropelle E, Cintra D, Pauli J. Exercise decreases CLK2 in the liver of obese mice and prevents hepatic fat accumulation. Journal Of Cellular Biochemistry 2018, 119: 5885-5892. PMID: 29575149, DOI: 10.1002/jcb.26780.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseObesity conditionsPrevention of NAFLDPhysical exerciseImpaired fat oxidationFatty liver diseaseMetabolic syndrome riskChronic physical exerciseHepatic fat accumulationAcid oxidationFatty acid oxidationObese groupLiver diseaseObese miceSwiss miceSyndrome riskFat accumulationObese animalsHepatic metabolismFat oxidationHepatic ketogenesisBeneficial effectsElevated levelsPotent strategyMice
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 panelAccumulationMiceOverexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
de Almeida Rodrigues B, Kuga G, Muñoz V, Gaspar R, Tavares M, Botezelli J, da Silva A, Cintra D, de Moura L, Simabuco F, Ropelle E, Pauli J. Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus. Neuroscience Letters 2017, 659: 14-17. PMID: 28866049, DOI: 10.1016/j.neulet.2017.08.067.Peer-Reviewed Original ResearchConceptsFoxO1 phosphorylationMKP-3 overexpressionDephosphorylation of FOXO1Potential therapeutic targetInjection of adenovirusOrexigenic neuropeptidesHypothalamic disorderHypothalamic third ventricleSwiss miceInsulin intracellularHypothalamic activationThird ventricleTherapeutic targetFoxO1 dephosphorylationAkt phosphorylationInsulin signalingImportant transcription factorDUSP6 geneHypothalamusSignificant reductionFOXO1MiceInsulin stimulationPresent studyInsulin signalHigh Dosage of Vitamin D Regulates the Energy Metabolism and Increases Insulin Sensitivity, but are Associated with High Levels of Kidney Damage
Gaspar R, Botezelli J, Kuga G, Muñoz V, Coope A, Pereira R, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. High Dosage of Vitamin D Regulates the Energy Metabolism and Increases Insulin Sensitivity, but are Associated with High Levels of Kidney Damage. Drug Development Research 2017, 78: 203-209. PMID: 28718949, DOI: 10.1002/ddr.21394.Peer-Reviewed Original ResearchConceptsMetabolic disordersHigh dosesRole of VitDVitamin D deficiencyImportant therapeutic targetD deficiencyRenal damageObese miceC57BL/6J miceInsulin sensitivityMetabolic benefitsTherapeutic strategiesTherapeutic targetVitDMiceDosesBody massDisordersLarge proportionCalcitriolObeseKidneyDiseaseDoseAdministration