2025
Exercise Pulmonary Hypertension and Beyond: Insights in Exercise Pathophysiology in Pulmonary Arterial Hypertension (PAH) from Invasive Cardiopulmonary Exercise Testing
Tarras E, Singh I, Kreiger J, Joseph P. Exercise Pulmonary Hypertension and Beyond: Insights in Exercise Pathophysiology in Pulmonary Arterial Hypertension (PAH) from Invasive Cardiopulmonary Exercise Testing. Journal Of Clinical Medicine 2025, 14: 804. PMID: 39941482, PMCID: PMC11818252, DOI: 10.3390/jcm14030804.Peer-Reviewed Original ResearchInvasive cardiopulmonary exercise testingPulmonary arterial hypertensionCardiopulmonary exercise testingArterial hypertensionAssociated with pulmonary vascular remodelingExercise testRight heart failureExercise pulmonary hypertensionPulmonary vascular remodelingPulmonary hypertensionProgressive diseasePulmonary vasculatureTherapeutic optionsExercise pathophysiologyHigh morbidityHeart failureEarly diagnosisVascular remodelingTherapeutic approachesPersonalized treatmentHypertensionDisease subtypesDiagnosisSkeletal muscleDiseaseSkeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes
do A H Souza A, Troschel A, Marquardt J, Hadžić I, Foldyna B, Moura F, Hainer J, Divakaran S, Blankstein R, Dorbala S, Di Carli M, Aerts H, Lu M, Fintelmann F, Taqueti V. Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes. European Heart Journal 2025, 46: 1112-1123. PMID: 39827905, DOI: 10.1093/eurheartj/ehae827.Peer-Reviewed Original ResearchCoronary microvascular dysfunctionBody mass indexCoronary flow reserveIntermuscular adipose tissueSubcutaneous adipose tissueHeart failureFat infiltrationMarker of coronary microvascular dysfunctionPRESERVED LEFT VENTRICULAR EJECTION FRACTIONCardiovascular outcomesAssociated with coronary microvascular dysfunctionHigher IMATIncreased IMATPresence of coronary microvascular dysfunctionSkeletal muscleFlow reserveIncreased risk of MACEMyocardial infarctionStress positron emission tomographyAssociated with increased MACERisk of heart failureLow coronary flow reserveThoracic vertebra levelVentricular ejection fractionIntermuscular adipose tissue area
2024
Development of a 31P magnetic resonance spectroscopy technique to quantify NADH and NAD+ at 3 T
Mevenkamp J, Bruls Y, Mancilla R, Grevendonk L, Wildberger J, Brouwers K, Hesselink M, Schrauwen P, Hoeks J, Houtkooper R, Buitinga M, de Graaf R, Lindeboom L, Schrauwen-Hinderling V. Development of a 31P magnetic resonance spectroscopy technique to quantify NADH and NAD+ at 3 T. Nature Communications 2024, 15: 9159. PMID: 39443469, PMCID: PMC11499639, DOI: 10.1038/s41467-024-53292-4.Peer-Reviewed Original ResearchConceptsPhysically active older adultsActive older adultsMetabolic healthHuman skeletal musclePhosphorous magnetic resonance spectroscopySedentary individualsOlder adultsStimulate mitochondrial biogenesisHealthSkeletal muscleMitochondrial biogenesisNAD+Physiological decreaseNADH contentNADHQuantify NADHClinical 3Magnetic resonance spectroscopy techniquesMR sequencesAdultsMeasurement reproducibilityThe Australian Genomics Mitochondrial Flagship: A national program delivering mitochondrial diagnoses
Rius R, Compton A, Baker N, Balasubramaniam S, Best S, Bhattacharya K, Boggs K, Boughtwood T, Braithwaite J, Bratkovic D, Bray A, Brion M, Burke J, Casauria S, Chong B, Coman D, Cowie S, Cowley M, de Silva M, Delatycki M, Edwards S, Ellaway C, Fahey M, Finlay K, Fletcher J, Frajman L, Frazier A, Gayevskiy V, Ghaoui R, Goel H, Goranitis I, Haas M, Hock D, Howting D, Jackson M, Kava M, Kemp M, King-Smith S, Lake N, Lamont P, Lee J, Long J, MacShane M, Madelli E, Martin E, Marum J, Mattiske T, McGill J, Metke A, Murray S, Panetta J, Phillips L, Quinn M, Ryan M, Schenscher S, Simons C, Smith N, Stroud D, Tchan M, Tom M, Wallis M, Ware T, Welch A, Wools C, Wu Y, Christodoulou J, Thorburn D. The Australian Genomics Mitochondrial Flagship: A national program delivering mitochondrial diagnoses. Genetics In Medicine 2024, 27: 101271. PMID: 39305161, DOI: 10.1016/j.gim.2024.101271.Peer-Reviewed Original ResearchGenome sequencePhenocopy genesMitochondrial diseaseMtDNA sequencesMtDNA deletionsMD geneMtDNAChildhood-onset diseaseDiagnostic journeyDiagnostic yieldMolecular diagnosisGenesNational studySequenceGene etiologySuspected MDDiagnostic pathwayIncrease diagnostic yieldPediatric-onsetOnset diseaseAdult onsetAdult patientsChildrenSkeletal muscleScoresEffects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi‐centre factorial randomized trial
Brown J, Spielmann G, Yang S, Compton S, Jones L, Irwin M, Ligibel J, Meyerhardt J. Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi‐centre factorial randomized trial. Journal Of Cachexia Sarcopenia And Muscle 2024, 15: 1520-1527. PMID: 38887915, PMCID: PMC11294014, DOI: 10.1002/jcsm.13509.Peer-Reviewed Original ResearchAerobic exerciseMyokine concentrationsStage I-III breastColorectal cancer survivorsEffects of exerciseColorectal cancerLinear mixed-effects regression modelsMixed-effects regression modelsCancer survivorsPhysical activityType I error rateExerciseMyokinesPilot studyRegression modelsCancer patientsRandomized trialsHypothesis-generating analysisMultiple comparisonsBreastSkeletal muscleInterleukin-15Clinical outcomesCancerPatientsImmunological regulation of skeletal muscle adaptation to exercise
Langston P, Mathis D. Immunological regulation of skeletal muscle adaptation to exercise. Cell Metabolism 2024, 36: 1175-1183. PMID: 38670108, PMCID: PMC11153001, DOI: 10.1016/j.cmet.2024.04.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsExercise immunologyBenefits of exerciseSkeletal muscle adaptationEffects of exerciseResponse to exerciseMaintenance of muscle homeostasisExercise adaptationMuscle adaptationExercise physiologyExercising muscleMusculoskeletal diseasesExerciseMuscle injuryMuscleSkeletal muscleHealth-promoting effectsMuscle biologyImmunological regulationExertionMuscle homeostasisExperimental muscle injuryConceptual frameworkImmunological basisSymptomsAgeSkeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α
Liu B, Xie D, Huang X, Jin S, Dai Y, Sun X, Li D, Bennett A, Diano S, Huang Y. Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α. Diabetologia 2024, 67: 724-737. PMID: 38216792, PMCID: PMC10904493, DOI: 10.1007/s00125-023-06073-5.Peer-Reviewed Original ResearchConceptsTen-eleven translocationMuscle insulin sensitivityRNA-seqPGC-1aRegulation of muscle insulin sensitivityType 2 diabetesAnalysis of RNA-seqResponse to environmental cuesGenome-wide expression profilingWild-typeHFD-fedHFD-induced insulin resistanceHigh-fat diet (HFD)-inducedExpression levelsMaintenance of glucoseSkeletal muscle insulin sensitivityAccession numbersSkeletal muscleEnhanced glucose toleranceFamily dioxygenasesMitochondrial respirationSkeletal muscle of humansEnvironmental cuesMitochondrial functionBiological processes
2023
Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism
Cohen J, Huang S, Koczwara K, Woods K, Ho V, Woodman K, Arbiser J, Daman K, Lek M, Emerson C, DeSimone A. Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism. Cell Death & Disease 2023, 14: 749. PMID: 37973788, PMCID: PMC10654915, DOI: 10.1038/s41419-023-06257-2.Peer-Reviewed Original ResearchConceptsMTOR-independent mechanismsFacioscapulohumeral muscular dystrophyDUX4 transcriptsDUX4 activityMultiple signal transduction pathwaysSignal transduction pathwaysTherapeutic developmentDUX4 proteinDUX4 expressionTransduction pathwaysPolyadenylation sitesChromosome 4DUX4 geneMechanisms of toxicityAutophagy pathwayExpression of ULK1DUX4Cellular autophagyCell deathRelevant pathwaysMuscular dystrophyMolecular methodsPathwaySkeletal muscleTranscriptsRegulatory T cells shield muscle mitochondria from interferon-γ–mediated damage to promote the beneficial effects of exercise
Langston P, Sun Y, Ryback B, Mueller A, Spiegelman B, Benoist C, Mathis D. Regulatory T cells shield muscle mitochondria from interferon-γ–mediated damage to promote the beneficial effects of exercise. Science Immunology 2023, 8: eadi5377. PMID: 37922340, PMCID: PMC10860652, DOI: 10.1126/sciimmunol.adi5377.Peer-Reviewed Original ResearchConceptsHealth activitiesPerformance-enhancing effectsEffects of exercise trainingEffects of exerciseResponse to exerciseChronic exercise modelsExercise trainingPhysical performanceExercise modelType 2 diabetesExerciseCD4<sup>+</sup> regulatory T cellsCardiovascular diseaseFoxp3<sup>+</sup>CD4<sup>+</sup> regulatory T cellsRegulatory T cellsSkeletal muscleT cellsInterferon-gMuscle mitochondriaEffector mechanismsMuscleInflammatory responseTherapeutic potentialDementiaMetabolic disruptionEffect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH
Insogna K, Sullivan R, Parziale S, Deng Y, Carrano D, Simpson C, Dufour S, Carpenter T, Petersen K. Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH. The Journal Of Clinical Endocrinology & Metabolism 2023, 109: e1061-e1071. PMID: 37930769, PMCID: PMC12102717, DOI: 10.1210/clinem/dgad642.Peer-Reviewed Original ResearchSymptoms of painMuscle function testsFunction testsMuscle strengthMuscle functionSkeletal muscleLower extremity joint painSTS testMuscle function studiesImproved muscle functionTreatment-naïve adultsSynthesis rateMonths of studyJoint painThird doseSymptomatic adultsClinical trialsRight calfATP synthesis rateBurosumabPainMuscle concentrationsXLHSymptomsMuscleThe Effect of Aerobic Exercise on SREBP-1c Gene Expression in Skeletal Muscle in Obese Female Rats
Eftekharzadeh M, Atashak S, Azarbayjani M, Moradi L, Rahmati-Ahmadabad S. The Effect of Aerobic Exercise on SREBP-1c Gene Expression in Skeletal Muscle in Obese Female Rats. Thrita 2023, 12 DOI: 10.5812/thrita-138382.Peer-Reviewed Original ResearchEffects of aerobic exerciseAerobic exerciseHigh-fat dietSkeletal muscle metabolic disordersObese female ratsTreadmill 5 timesInteractive effects of aerobic exerciseMuscle metabolic disordersHigh-fatFemale ratsAerobic trainingSkeletal muscleQuadriceps muscleSREBP-1c geneSREBP-1c gene expressionNormal dietTraining sessionsMetabolic disordersExerciseSterol regulatory element-binding proteinFemale Wistar ratsWeight of ratsLipid metabolismQuadricepsSREBP-1cP299 Over-expression of FKRP in heart induces myocarditis and dilated cardiomyopathy in LGMD2I/R9 mice
Huang S, Ma K, Cohen J, Ho V, Xu J, Gauthier L, O'Connor C, Ge L, Woodman K, Lek M. P299 Over-expression of FKRP in heart induces myocarditis and dilated cardiomyopathy in LGMD2I/R9 mice. Neuromuscular Disorders 2023, 33: s118. DOI: 10.1016/j.nmd.2023.07.209.Peer-Reviewed Original ResearchGene replacement therapyReplacement therapySkeletal muscleFKRP geneLeft ventricular cavity sizeEvidence of myocarditisHigh expressionLow ejection fractionVentricular cavity sizeAutosomal recessive disorderCardiac involvementEjection fractionInflammatory infiltrationCardiac statusCardiac outputFatal cardiotoxicityFatal myocarditisDosed miceInclusion criteriaHeart sectionsMouse modelDystrophic miceDystrophic pathologyFKRP mutationsPatientsBody Composition, Coronary Microvascular Dysfunction, and Future Risk of Cardiovascular Events Including Heart Failure
Souza A, Rosenthal M, Moura F, Divakaran S, Osborne M, Hainer J, Dorbala S, Blankstein R, Di Carli M, Taqueti V. Body Composition, Coronary Microvascular Dysfunction, and Future Risk of Cardiovascular Events Including Heart Failure. JACC Cardiovascular Imaging 2023, 17: 179-191. PMID: 37768241, PMCID: PMC10922555, DOI: 10.1016/j.jcmg.2023.07.014.Peer-Reviewed Original ResearchConceptsCoronary microvascular dysfunctionVisceral adipose tissueAssociated with coronary microvascular dysfunctionCoronary flow reserveBody mass indexLow coronary flow reserveSubcutaneous adipose tissueCoronary artery diseaseAdverse eventsPositron emission tomographyObese patientsMicrovascular dysfunctionVisceral adipose tissue cross-sectional areaCardiovascular eventsHeart failurePRESERVED LEFT VENTRICULAR EJECTION FRACTIONAdverse outcomesSkeletal muscleArtery diseaseFlow-limiting coronary artery diseaseBody compositionAssociated with body compositionEvaluation of coronary artery diseaseStress positron emission tomographyEmission tomography191-OR: Deletion of the Type 2 Diabetes Candidate Gene SLC16A11 Reduces Peripheral Insulin Sensitivity in Mice
EL-AGROUDY N, SCHUMANN T, KURZBACH A, SANCAR G, SANDFORTH L, HERRMANN C, SHULMAN G, BIRKENFELD A. 191-OR: Deletion of the Type 2 Diabetes Candidate Gene SLC16A11 Reduces Peripheral Insulin Sensitivity in Mice. Diabetes 2023, 72 DOI: 10.2337/db23-191-or.Peer-Reviewed Original ResearchDb/db miceOb/obInsulin sensitivityDb miceMRNA expressionWhole-body insulin sensitivitySkeletal muscle insulin sensitivitySkeletal muscle insulin resistanceSkeletal musclePeripheral insulin sensitivityTreatment of T2D.Hyperinsulinemic-euglycemic clampLiver fat contentGlucose infusion rateMuscle insulin sensitivityMuscle insulin resistanceHepatic glucose productionHepatic mitochondrial functionWT littermate miceThe Potential Role of PET in the Management of Peripheral Artery Disease
Alashi A, Vermillion B, Sinusas A. The Potential Role of PET in the Management of Peripheral Artery Disease. Current Cardiology Reports 2023, 25: 831-839. PMID: 37314651, PMCID: PMC11542486, DOI: 10.1007/s11886-023-01904-8.Peer-Reviewed Original ResearchConceptsPeripheral artery diseaseArtery diseaseLower extremitiesManagement of PADSetting of PADEarly detectionLarge vessel diseaseManagement of patientsNon-invasive testsPositron emission tomography (PET) imagingEmission Tomography ImagingNon-invasive toolVascular inflammationVessel diseaseMicrovascular perfusionRoutine screeningBlood flowClinical researchPatientsDiseaseTomography imagingPET imagingSkeletal musclePotential roleSummaryThe purposeElectrical impedance myography detects age-related skeletal muscle atrophy in adult zebrafish
Rutkove S, Callegari S, Concepcion H, Mourey T, Widrick J, Nagy J, Nath A. Electrical impedance myography detects age-related skeletal muscle atrophy in adult zebrafish. Scientific Reports 2023, 13: 7191. PMID: 37137956, PMCID: PMC10156759, DOI: 10.1038/s41598-023-34119-6.Peer-Reviewed Original ResearchConceptsAge-related skeletal muscle atrophyMuscle functionLoss of muscle massAssociated with fallsSkeletal muscle atrophyEvaluate potential therapeuticsSkeletal muscle functionTotal muscle areaMechanism of muscle degenerationClinical studiesMuscle atrophyMuscle degenerationMuscle healthMuscle massElectrical impedance myographyReplication cohortBioelectric propertiesFunctional declineNeuromuscular disordersSkeletal muscleDisease mechanismsImpedance myographySarcopeniaMuscle areaAge-related deficitsAn observational human study investigating the effect of anabolic androgenic steroid use on the transcriptome of skeletal muscle and whole blood using RNA-Seq
Kolliari-Turner A, Lima G, Wang G, Malinsky F, Karanikolou A, Eichhorn G, Tanisawa K, Ospina-Betancurt J, Hamilton B, Kumi P, Shurlock J, Skiadas V, Twycross-Lewis R, Kilduff L, Martin R, Ash G, Potter C, Guppy F, Seto J, Fossati C, Pigozzi F, Borrione P, Pitsiladis Y. An observational human study investigating the effect of anabolic androgenic steroid use on the transcriptome of skeletal muscle and whole blood using RNA-Seq. BMC Medical Genomics 2023, 16: 94. PMID: 37138349, PMCID: PMC10157927, DOI: 10.1186/s12920-023-01512-z.Peer-Reviewed Original ResearchConceptsAnabolic androgenic steroidsWhole bloodWhole blood transcriptional signaturesBlood transcriptional signaturesSkeletal muscleTranscriptional signatureObservational human studiesLong-term cessationAnabolic-androgenic steroid useSteroid useAAS exposureSedentary controlsAndrogen receptorBackgroundThe effectsHuman studiesHypertrophic processAndrogenic steroidsHuman whole bloodAAS usersBloodGroup comparisonsTime pointsTraining regimensMuscleAAS usageThe Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties
Jiang R, Roy B, Wu Q, Mohanty S, Nowak R, Shaw A, Kleinstein S, O’Connor K. The Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties. ImmunoHorizons 2023, 7: 310-322. PMID: 37171806, PMCID: PMC10579972, DOI: 10.4049/immunohorizons.2200078.Peer-Reviewed Original ResearchConceptsInclusion body myositisMemory B cellsCell infiltrateBody myositisB cellsIBM muscle biopsiesB-cell infiltratesPlasma cell infiltrateClass-switched IgGMuscle tissueAdaptive immune receptor repertoire sequencingHumoral responseHealthy controlsIgA isotypePlasma cellsCell repertoireMuscle biopsyInfiltratesDegenerative disordersDisease pathologyRepertoire sequencingSkeletal muscleDermatomyositisPolymyositisMyositisEffects 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 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
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