2023
Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition
Sakuma I, Gaspar R, Luukkonen P, Kahn M, Zhang D, Zhang X, Murray S, Golla J, Vatner D, Samuel V, Petersen K, Shulman G. Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2312666120. PMID: 38127985, PMCID: PMC10756285, DOI: 10.1073/pnas.2312666120.Peer-Reviewed Original Research
2022
Short-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
2020
A Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance
Lyu K, Zhang Y, Zhang D, Kahn M, Ter Horst KW, Rodrigues MRS, Gaspar RC, Hirabara SM, Luukkonen PK, Lee S, Bhanot S, Rinehart J, Blume N, Rasch MG, Serlie MJ, Bogan JS, Cline GW, Samuel VT, Shulman GI. A Membrane-Bound Diacylglycerol Species Induces PKCϵ-Mediated Hepatic Insulin Resistance. Cell Metabolism 2020, 32: 654-664.e5. PMID: 32882164, PMCID: PMC7544641, DOI: 10.1016/j.cmet.2020.08.001.Peer-Reviewed Original ResearchConceptsPlasma membraneEndoplasmic reticulumHigh-fat diet-induced hepatic insulin resistanceSubcellular fractionation methodInsulin receptor kinaseKey lipid speciesHepatic insulin resistanceDiet-induced hepatic insulin resistanceReceptor kinaseDiacylglycerol acyltransferase 2Molecular mechanismsAcute knockdownPhosphorylationLipid dropletsLipid speciesAcyltransferase 2KnockdownLiver-specific overexpressionDAG accumulationPKCϵDAG contentMembraneFractionation methodKinaseMitochondriaAging is associated with increased TRB3, ER stress, and hepatic glucose production in the liver of rats
Gaspar R, Muñoz V, Nakandakari S, Vieira R, da Conceição L, de Oliveira F, Crisol B, da Silva A, Cintra D, de Moura L, Ropelle E, Zaghloul I, Mekary R, Pauli J. Aging is associated with increased TRB3, ER stress, and hepatic glucose production in the liver of rats. Experimental Gerontology 2020, 139: 111021. PMID: 32659331, DOI: 10.1016/j.exger.2020.111021.Peer-Reviewed Original ResearchConceptsER stressEukaryotic translation initiation factorProtein kinase RNA-like endoplasmic reticulum kinaseRNA-like endoplasmic reticulum kinaseTranslation initiation factorPhosphorylation of inositolStress response regulationEndoplasmic reticulum kinaseEndoplasmic reticulum stress pathwayMammalian homologDrosophila tribblesEndoplasmic reticulum stressInitiation factorsProtein contentTRB3Multiple tissuesStress pathwaysImmunoglobulin proteinEnzymes of gluconeogenesisReticulum stressHepatic glucose productionEnzyme 1Response regulationMolecular changesPyruvate challengePhysical 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 Research
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 1Physical training reverses changes in hepatic mitochondrial diameter of Alloxan-induced diabetic rats
Kuga G, Gaspar R, Muñoz V, Nakandakari S, Breda L, Sandoval B, Caetano F, de Almeida Leme J, Pauli J, Gomes R. Physical training reverses changes in hepatic mitochondrial diameter of Alloxan-induced diabetic rats. Einstein (São Paulo) 2018, 16: eao4353. PMID: 30088548, PMCID: PMC6110382, DOI: 10.1590/s1679-45082018ao4353.Peer-Reviewed Original ResearchConceptsDiabetic ratsBody weightDiabetic groupSedentary diabeticDiabetic animalsPhysical trainingSedentary diabetic animalsPhysical training protocolMitochondrial diameterDiabetes mellitusAlloxan administrationBlood insulinExercise protocolSerum glucoseSedentary controlsWistar ratsHepatic metabolismReverses changesLiver glycogenHepatic glycogenDiabeticsRatsMeasurements of glycogenLiver samplesTraining protocolImpaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B
Kuga G, Muñoz V, Gaspar R, Nakandakari S, da Silva A, Botezelli J, Leme J, Gomes R, de Moura L, Cintra D, Ropelle E, Pauli J. Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B. Experimental Gerontology 2018, 104: 66-71. PMID: 29421605, DOI: 10.1016/j.exger.2018.02.005.Peer-Reviewed Original ResearchConceptsMiddle-aged ratsBrain-derived neurotrophic factorΒ-amyloid contentAlzheimer's diseaseInsulin resistanceTau phosphorylationMorris water maze testMiddle-aged Wistar ratsInsulin tolerance testMain risk factorsAge-related changesNeurotrophic factorTolerance testRisk factorsMaze testImpaired insulinWistar ratsNew therapiesHippocampus regionBody weightCognitive declineRole of PTP1BSynaptic plasticityRatsSpatial learning