2025
AI-based volumetric six-tissue body composition quantification from CT cardiac attenuation scans for mortality prediction: a multicentre study
Yi J, Marcinkiewicz A, Shanbhag A, Miller R, Geers J, Zhang W, Killekar A, Manral N, Lemley M, Buchwald M, Kwiecinski J, Zhou J, Kavanagh P, Liang J, Builoff V, Ruddy T, Einstein A, Feher A, Miller E, Sinusas A, Berman D, Dey D, Slomka P. AI-based volumetric six-tissue body composition quantification from CT cardiac attenuation scans for mortality prediction: a multicentre study. The Lancet Digital Health 2025, 7: 100862. PMID: 40382274, PMCID: PMC12126277, DOI: 10.1016/j.landig.2025.02.002.Peer-Reviewed Original ResearchConceptsCT attenuation correctionEpicardial adipose tissueVisceral adipose tissuePrognostic valueAdipose tissuePerfusion imagingMedian follow-up timeHigher visceral adipose tissueIncreased all-cause mortality riskMuscle volume indexAttenuation correctionPredicting all-cause mortalityCardiac perfusion imagingKaplan-Meier curvesAll-cause mortality riskBody composition measurementsCox regression modelsAll-cause mortalityReduced riskVolumetric measurementsIntramuscular adipose tissueMortality risk stratificationAI-based segmentationSubcutaneous adipose tissueIndex volumeATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis
Slusher A, Santoro N, Vash-Margita A, Galderisi A, Hu P, Tokoglu F, Li Z, Tarabra E, Strober J, Vatner D, Shulman G, Caprio S. ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis. Journal Of Clinical Investigation 2025, 135: e184740. PMID: 40091831, PMCID: PMC11910223, DOI: 10.1172/jci184740.Peer-Reviewed Original ResearchConceptsHyperinsulinemic-euglycemic clampSubcutaneous adipose tissueInsulin resistanceAdipose triglyceride lipaseInsulin infusionOral glucose tolerance testAbdominal fat distributionGlucose tolerance testMeasuring abdominal fat distributionLower liver fatActivating adipose triglyceride lipaseMetabolic disease riskLiver fat contentEctopic lipid storageFUNDINGThis workAdipose tissue lipolysisInhibition of adipose tissue lipolysisSubcutaneous adipose tissue samplesFat distributionTolerance testInsulin exposureLiver fatInfusionGlycerol turnoverAdipose tissueSkeletal 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 areaFGF21 regulates ceramide levels preferentially in visceral vs. subcutaneous white adipose tissue in aged mice fed a high-fat diet
Gliniak C, Gordillo R, Field B, Dixit V, Scherer P. FGF21 regulates ceramide levels preferentially in visceral vs. subcutaneous white adipose tissue in aged mice fed a high-fat diet. Physiology 2025, 40: 1588. DOI: 10.1152/physiol.2025.40.s1.1588.Peer-Reviewed Original Research
2024
Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity
Galuppo B, Mannam P, Bonet J, Pierpont B, Trico’ D, Haskell-Luevano C, Ericson M, Freeman K, Philbrick W, Bale A, Caprio S, Santoro N. Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity. International Journal Of Obesity 2024, 49: 819-826. PMID: 39738493, PMCID: PMC12095050, DOI: 10.1038/s41366-024-01706-0.Peer-Reviewed Original ResearchOral glucose tolerance testVisceral adipose tissueMelanocortin-4 receptor geneSubcutaneous adipose tissueVariant groupYale Pediatric Obesity ClinicInsulin resistanceEarly-onset obesityBMI z-scorePediatric obesity clinicRare variantsAdipose tissueAbdominal fat distributionDegree of obesityGlucose tolerance testTotal body fatIntrahepatic fat contentLower insulin sensitivityIntrahepatic fat accumulationAssociated with abdominal fatAbdominal MRIObesity clinicMetabolic sequelaePathogenic variantsFat distributionInsulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial
Nadeau K, Arslanian S, Bacha F, Caprio S, Chao L, Farrell R, Hughan K, Rayas M, Tung M, Cross K, El ghormli L. Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial. Diabetologia 2024, 68: 676-687. PMID: 39706874, DOI: 10.1007/s00125-024-06327-w.Peer-Reviewed Original ResearchConceptsYouth-onset type 2 diabetesType 2 diabetesBeta cell functionRandomised clinical trialsVisceral adipose tissueMarkers of adiposityInsulin sensitivityInsulin clearanceSubcutaneous adipose tissueCell functionClinical trialsResponse to rosiglitazone treatmentDual-energy X-ray absorptiometryPersistently elevated blood glucose levelsMarkers of insulin sensitivityFasting blood testsX-ray absorptiometryFasting C-peptideNon-Hispanic black raceAdipose tissueResponse to treatmentCompensatory response to changesElevated blood glucose levelsNational Institute of DiabetesSecondary analysisThe subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose
Mashayekhi M, Sheng Q, Bailin S, Massier L, Zhong J, Shi M, Wanjalla C, Wang T, Ikizler T, Niswender K, Gabriel C, Palacios J, Turgeon‐Jones R, Reynolds C, Luther J, Brown N, Das S, Dahlman I, Mosley J, Koethe J, Rydén M, Bachmann K, Shah R. The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose. Obesity 2024, 32: 1526-1540. PMID: 38967296, PMCID: PMC11269023, DOI: 10.1002/oby.24064.Peer-Reviewed Original ResearchVisceral adipose tissueExpression quantitative trait lociSubcutaneous adipose tissueGenetic effect sizesQuantitative trait lociInsulin resistanceAdipocyte transcriptsSat geneAdipose transcriptomeTrait lociTranscriptional architectureTranscriptional landscapeMetabolic bufferRNA sequencingInsulin stimulationAdipose tissueNon-immune cell populationsMetabolic phenotypeWeight loss surgeryNon-immune populationSpectrum of obesityCardiometabolic disease riskMacrophage transcriptionMolecular signaturesType 2 diabetesAltered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity
Slusher A, Nouws J, Tokoglu F, Vash‐Margita A, Matthews M, Fitch M, Shankaran M, Hellerstein M, Caprio S. Altered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity. Obesity 2024, 32: 593-602. PMID: 38410080, PMCID: PMC11034857, DOI: 10.1002/oby.23974.Peer-Reviewed Original ResearchConceptsSubcutaneous adipose tissueLiver fat contentInsulin resistanceInsulin sensitivityEctopic storage of lipidOral glucose tolerance testGluteal subcutaneous adipose tissueExtracellular matrix dynamicsMagnetic resonance imaging scansAdipose tissueBody fat distribution patternsFibrogenesis in vivoAdipocyte turnoverAssociated with insulin resistanceGlucose tolerance testFat distribution patternsWhole-body IRAdipose tissue insulin signalingTissue insulin signalingTolerance testGluteal fatImaging scansPathophysiological pathwaysAssociated with ratioObesity
2023
FRI032 Cellular Insights Into Metabolically Healthy And Unhealthy Obesity
Petersen M, Smith G, Yu J, Barve R, Yoshino J, Shulman G, Klein S. FRI032 Cellular Insights Into Metabolically Healthy And Unhealthy Obesity. Journal Of The Endocrine Society 2023, 7: bvad114.043. PMCID: PMC10555440, DOI: 10.1210/jendso/bvad114.043.Peer-Reviewed Original ResearchAbdominal subcutaneous adipose tissueWhole-body insulin sensitivityInsulin sensitivityMUO groupMuscle ceramide contentCeramide contentAdipose tissueGreater whole-body insulin sensitivityPlasma C-peptide concentrationC-peptide concentrationsAdverse metabolic effectsSubcutaneous adipose tissueExpression of genesSkeletal muscle expressionMitochondrial content/functionHealthy obesityMitochondrial structure/functionSkeletal muscle diacylglycerolUnhealthy obesityExtracellular matrix remodelingExcess adiposityMHL groupMetabolic effectsMuscle diacylglycerolInsulin actionBody 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 tomographyQuantification of cell energetics in human subcutaneous adipose progenitor cells after target gene knockdown
Li L, Gunewardena A, Nyima T, Feldman B. Quantification of cell energetics in human subcutaneous adipose progenitor cells after target gene knockdown. STAR Protocols 2023, 4: 102607. PMID: 37742183, PMCID: PMC10751552, DOI: 10.1016/j.xpro.2023.102607.Peer-Reviewed Original ResearchDeep learning of image-derived measures of body composition in pediatric, adolescent, and young adult lymphoma: association with late treatment effects
Tram N, Chou T, Janse S, Bobbey A, Audino A, Onofrey J, Stacy M. Deep learning of image-derived measures of body composition in pediatric, adolescent, and young adult lymphoma: association with late treatment effects. European Radiology 2023, 33: 6599-6607. PMID: 36988714, DOI: 10.1007/s00330-023-09587-z.Peer-Reviewed Original ResearchConceptsProportional hazards regression analysisHazards regression analysisLate effectsBody composition measuresAYA patientsHigh riskBody compositionCox proportional hazards regression analysisTreatment-related late effectsComposition measuresCancer treatmentSerious adverse eventsLate treatment effectsYoung adult patientsSubcutaneous adipose tissueRegression analysisCare CT imagesSingle-site studyMuscle tissueAdult patientsAdverse eventsInitial stagingPediatric patientsAdult lymphomasPrognostic value
2022
Obesity aggravates contact hypersensitivity reaction in mice
Majewska‐Szczepanik M, Kowalczyk P, Marcińska K, Strzępa A, Lis GJ, Wong FS, Szczepanik M, Wen L. Obesity aggravates contact hypersensitivity reaction in mice. Contact Dermatitis 2022, 87: 28-39. PMID: 35234303, PMCID: PMC9949724, DOI: 10.1111/cod.14088.Peer-Reviewed Original ResearchConceptsContact hypersensitivityFecal microbiota transplantationQuantitative polymerase chain reactionIL-17AObese miceEnhanced contact hypersensitivityGut microbiota dysbiosisLow-grade inflammationContact hypersensitivity reactionInfluence of obesityInflammatory skin diseaseT helper 1Antigen-specific responsesHigh-fat dietSubcutaneous adipose tissueProinflammatory CD4Proinflammatory milieuCytokine profileMicrobiota dysbiosisDendritic cellsLymph nodesMicrobiota transplantationHelper 1Hypersensitivity reactionsImmune cells
2020
The omentum of obese girls harbors small adipocytes and browning transcripts
Tarabra E, Nouws J, Vash-Margita A, Nadzam GS, Goldberg-Gell R, Van Name M, Pierpont B, Knight J, Shulman GI, Caprio S. The omentum of obese girls harbors small adipocytes and browning transcripts. JCI Insight 2020, 5 PMID: 32125283, PMCID: PMC7213797, DOI: 10.1172/jci.insight.135448.Peer-Reviewed Original ResearchConceptsSubcutaneous adipose tissueSAT depotsSleeve gastrectomySevere obesityInsulin resistanceInsulin sensitivitySmall adipocytesAdipose tissueAbdominal subcutaneous adipose tissueWeight lossType 2 diabetesOmental adipose tissueSubgroup of subjectsTranscriptomic profilesSAT biopsiesAdipocyte sizeObese girlsCardiovascular diseaseContribution of Sonoelastography to Diagnosis in Distinguishing Benign and Malignant Breast Masses
Yıldız M, Goya C, Adin M. Contribution of Sonoelastography to Diagnosis in Distinguishing Benign and Malignant Breast Masses. Journal Of Ultrasound In Medicine 2020, 39: 1395-1403. PMID: 32083349, DOI: 10.1002/jum.15236.Peer-Reviewed Original ResearchConceptsB-mode ultrasoundStrain indexMalignant lesionsBenign lesionsSonoelastographic examinationBreast massesMean strain indexDiagnostic performanceMean strain index valueSubcutaneous adipose tissueStrain index valueFemale patientsMean ageHistopathologic evaluationHistopathologic findingsScoring methodDifferential diagnosisAdipose tissueDistinguishing BenignUnnecessary biopsiesDiagnostic efficacyLesionsSolid breast massesMalignant breast massesDiagnostic accuracy
2019
Altered In Vivo Lipid Fluxes and Cell Dynamics in Subcutaneous Adipose Tissues Are Associated With the Unfavorable Pattern of Fat Distribution in Obese Adolescent Girls
Nouws J, Fitch M, Mata M, Santoro N, Galuppo B, Kursawe R, Narayan D, Vash-Margita A, Pierpont B, Shulman GI, Hellerstein M, Caprio S. Altered In Vivo Lipid Fluxes and Cell Dynamics in Subcutaneous Adipose Tissues Are Associated With the Unfavorable Pattern of Fat Distribution in Obese Adolescent Girls. Diabetes 2019, 68: 1168-1177. PMID: 30936147, PMCID: PMC6610014, DOI: 10.2337/db18-1162.Peer-Reviewed Original ResearchConceptsObese adolescent girlsFat distributionFatty liverMetabolic impairmentMature adipocytesAdipose tissueAbdominal fat distributionEctopic fat distributionFemoral adipose tissueType 2 diabetesAdolescent girlsDe novo lipogenesisSubcutaneous adipose tissueVascular cell proliferationUnfavorable phenotypeSubcutaneous abdominalAdipose lipidsInsulin resistanceObese adolescentsUnderlying metabolic alterationsObese girlsHigh riskNovo lipogenesisGluteal depotMetabolic alterationsAdipose Tissue in Persons With HIV Is Enriched for CD4+ T Effector Memory and T Effector Memory RA+ Cells, Which Show Higher CD69 Expression and CD57, CX3CR1, GPR56 Co-expression With Increasing Glucose Intolerance
Wanjalla CN, McDonnell WJ, Barnett L, Simmons JD, Furch BD, Lima MC, Woodward BO, Fan R, Fei Y, Baker PG, Ram R, Pilkinton MA, Mashayekhi M, Brown NJ, Mallal SA, Kalams SA, Koethe JR. Adipose Tissue in Persons With HIV Is Enriched for CD4+ T Effector Memory and T Effector Memory RA+ Cells, Which Show Higher CD69 Expression and CD57, CX3CR1, GPR56 Co-expression With Increasing Glucose Intolerance. Frontiers In Immunology 2019, 10: 408. PMID: 30941121, PMCID: PMC6433850, DOI: 10.3389/fimmu.2019.00408.Peer-Reviewed Original ResearchConceptsHIV-negative controlsSubcutaneous adipose tissueT effector memoryAdipose tissueMemory CD45ROEffector memoryGlucose intoleranceMemory subsetsT cellsChronic T cell activationProgressive glucose intoleranceAdipose tissue inflammationT cell profileDistribution of CD4T cell expressionHigher CD69 expressionSimilar glucose toleranceT cell activationWhole adipose tissueCD4 ratioHIV infectionImmune senescenceGlucose toleranceHIV statusCardiometabolic diseasesIncreased Diet Quality is Associated with Long‐Term Reduction of Abdominal and Pericardial Fat
Hennein R, Liu C, McKeown NM, Hoffmann U, Long MT, Levy D, Ma J. Increased Diet Quality is Associated with Long‐Term Reduction of Abdominal and Pericardial Fat. Obesity 2019, 27: 670-677. PMID: 30825267, PMCID: PMC6430652, DOI: 10.1002/oby.22427.Peer-Reviewed Original ResearchConceptsMediterranean-style diet scoreLess fat accumulationGenetic risk scoreFat accumulationDiet qualityAdipose tissueAbdominal subcutaneous adipose tissueEctopic fat depotsEctopic fat accumulationGenetic riskFramingham Heart Study participantsVisceral adipose tissuePericardial adipose tissueSubcutaneous adipose tissueDiet scorePericardial fatLong-term reductionRisk scoreFat depotsAdiposity profilesStudy participantsSD improvementFavorable changesLongitudinal associationsLongitudinal improvement
2016
A glucocorticoid- and diet-responsive pathway toggles adipocyte precursor cell activity in vivo
Wong J, Krueger K, Costa M, Aggarwal A, Du H, McLaughlin T, Feldman B. A glucocorticoid- and diet-responsive pathway toggles adipocyte precursor cell activity in vivo. Science Signaling 2016, 9: ra103. PMID: 27811141, PMCID: PMC8087215, DOI: 10.1126/scisignal.aag0487.Peer-Reviewed Original ResearchConceptsDifferentiation of adipocyte precursor cellsAdipocyte precursor cellsCell activity in vivoAdipose depotsADAMTS1 expressionDiet-induced weight gainAdipose tissueInguinal adipose depotsAdipocyte differentiation programExcess caloric intakeExtracellular protease ADAMTS1Pathogenesis of obesityAdipose tissue hyperplasiaExposure in vitroExpansion of adipose tissueWnt target genesWnt/b-catenin pathwayAdipose tissue homeostasisExpression of ADAMTS1High-fat dietSubcutaneous adipose tissueMouse subcutaneous adipose tissueSubcutaneous adipose depotsCaloric intakeTranscription factorsD‐dopachrome tautomerase in adipose tissue inflammation and wound repair
Kim B, Tilstam PV, Hwang SS, Simons D, Schulte W, Leng L, Sauler M, Ganse B, Averdunk L, Kopp R, Stoppe C, Bernhagen J, Pallua N, Bucala R. D‐dopachrome tautomerase in adipose tissue inflammation and wound repair. Journal Of Cellular And Molecular Medicine 2016, 21: 35-45. PMID: 27605340, PMCID: PMC5192814, DOI: 10.1111/jcmm.12936.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsAntigens, Differentiation, B-LymphocyteCell MovementCell ProliferationDown-RegulationFibroblastsHistocompatibility Antigens Class IIHumansInflammationIntramolecular OxidoreductasesMacrophagesMaleMiceMice, Inbred C57BLObesityReceptors, CXCR4Receptors, Interleukin-8BUp-RegulationWound HealingConceptsAdipose tissue inflammationSubcutaneous adipose tissueD-DTAdipose tissueTissue inflammationWound repairEpididymal fat padsDopachrome tautomeraseReceptor CXCR2MIF antibodyInflammatory cellsReceptor CD74Healthy donorsReceptor expressionFat padMRNA expressionProtein levelsWound healingFibroblast survivalMIFInflammationHealingTissueCell migrationFibroblast wound healing
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