2025
Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis
Sakuma I, Gaspar R, Nasiri A, Dufour S, Kahn M, Zheng J, LaMoia T, Guerra M, Taki Y, Kawashima Y, Yimlamai D, Perelis M, Vatner D, Petersen K, Huttasch M, Knebel B, Kahl S, Roden M, Samuel V, Tanaka T, Shulman G. Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2502978122. PMID: 40310463, DOI: 10.1073/pnas.2502978122.Peer-Reviewed Original ResearchConceptsCholine-deficient l-amino acid-defined high-fat dietBempedoic acidLiver fibrosisLiver diseaseL-amino acid-defined high-fat dietAdvanced liver diseaseCholesterol contentHSD17B13 variantsHigh-fat dietTotal liver cholesterol contentTreated miceActivate signaling pathwaysVariant rs738409Liver cholesterol contentLiver lipidsFibrotic responsePromote inflammationTherapeutic approachesSteatotic liver diseaseDietary cholesterol supplementationFibrosisHuman liver samplesI148MAntisense oligonucleotidesProgressive formNotch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice
Gaspar R, Macêdo A, Nakandakari S, Muñoz V, Abud G, Vieira R, de Sousa Neto I, Pavan I, da Silva L, Simabuco F, da Silva A, Salgado W, Marchini J, Nonino C, Cintra D, Ropelle E, Pajvani U, de Freitas E, Pauli J. Notch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice. Liver International 2025, 45: e70068. PMID: 40078075, DOI: 10.1111/liv.70068.Peer-Reviewed Original ResearchConceptsNotch1 signalingAerobic exerciseRegulation of hepatic glucoseObese miceImpact of aerobic exerciseEffects of Notch1 signalingAerobic exercise trainingMTORC1 pathway activationNotch1 pathwayObese individualsTissue of obese miceCross-sectional studyNotch1 mRNA levelsMitochondrial respirationExercise trainingLivers of obese individualsTreadmill runningGluconeogenic enzymesHepG2 cell lineLipid accumulationTraining groupHepatic glucoseHepatic metabolismNotch1 proteinPathway activation
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 factorsShort-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 ResearchMeSH KeywordsAdipose TissueAnimalsDiet, High-FatFatty Acids, Omega-3GlucoseInflammationLinseed OilMiceMice, Inbred C57BLConceptsControl 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 consumption
2021
Time‐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 ResearchMeSH KeywordsAnimalsDiet, High-FatInsulin ResistanceLiverMaleMetabolic DiseasesMiceMice, Inbred C57BLObesityWeight GainConceptsTime-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
2019
Short-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 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 1/2ObeseObesityExercise 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
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