2025
ATGL 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 tissue
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 distributionEstablishing feasibility and reliability of subcutaneous fat measurements by ultrasound in very preterm infants
Buck C, Santoro K, Shabanova V, Martin C, Taylor S. Establishing feasibility and reliability of subcutaneous fat measurements by ultrasound in very preterm infants. Pediatric Research 2024, 96: 1724-1731. PMID: 39069538, PMCID: PMC11772127, DOI: 10.1038/s41390-024-03439-2.Peer-Reviewed Original ResearchVery preterm infantsBody composition assessmentPreterm infantsPostmenstrual ageMarkers of metabolic healthFat distributionBedside ultrasoundCohort of very preterm infantsComposition assessmentWeeks' PMA,Metabolic healthIntra-rater intraclass correlation coefficientBrain growthBody composition metricsBody composition outcomesBedside ultrasound techniqueRegional fat distributionPoint of care ultrasoundIntraclass correlation coefficientPostmenstrual weeksMulticenter cohortRegional fatSubcutaneous fat distributionComposite outcomeSubcutaneous fat measurements
2023
Estradiol cycling drives female obesogenic adipocyte hyperplasia
del M. Saavedra-Peña R, Taylor N, Flannery C, Rodeheffer M. Estradiol cycling drives female obesogenic adipocyte hyperplasia. Cell Reports 2023, 42: 112390. PMID: 37053070, PMCID: PMC10567995, DOI: 10.1016/j.celrep.2023.112390.Peer-Reviewed Original ResearchConceptsAdipocyte precursor cellsHigh-fat dietAdipocyte hyperplasiaHFD feedingVisceral WATDifferential fat distributionAdipose tissue distributionEstrogen receptor αWAT distributionFat distributionOvariectomized femalesHyperplasiaMice showEstrous cycleReceptor αTissue distributionPrecursor cellsObesityAPC proliferationTissue microenvironmentProliferationFemalesSexOnsetFeeding
2022
The protective effect of rs373863828 on type 2 diabetes does not operate through a body composition pathway in adult Samoans
Hawley NL, Duckham RL, Carlson JC, Naseri T, Reupena MS, Lameko V, Pomer A, Wetzel A, Selu M, Lupematisila V, Unasa F, Vesi L, Fatu T, Unasa S, Faasalele‐Savusa K, Rivara AC, Russell E, Delany JP, Viali S, Kershaw EE, Minster RL, Weeks DE, McGarvey ST. The protective effect of rs373863828 on type 2 diabetes does not operate through a body composition pathway in adult Samoans. Obesity 2022, 30: 2468-2476. PMID: 36284436, PMCID: PMC10111239, DOI: 10.1002/oby.23559.Peer-Reviewed Original ResearchConceptsFat-free massType 2 diabetesFat distributionProtective effectBody compositionFavorable body fat distributionDual-energy X-ray absorptiometry-derived body compositionBody fat distributionGreater fat-free massPercent body fatBody size/compositionAssociation of genotypesRs373863828 genotypeVisceral adiposityHigher BMIAdult SamoansRole of fatGreater BMILean massBody fatLower oddsParadoxical associationTissue-specific mechanismsA alleleDiabetes
2021
CIDEA expression in SAT from adolescent girls with obesity and unfavorable patterns of abdominal fat distribution
Tarabra E, Nouws J, Vash‐Margita A, Hellerstein M, Shabanova V, McCollum S, Pierpont B, Zhao D, Shulman GI, Caprio S. CIDEA expression in SAT from adolescent girls with obesity and unfavorable patterns of abdominal fat distribution. Obesity 2021, 29: 2068-2080. PMID: 34672413, PMCID: PMC8612981, DOI: 10.1002/oby.23295.Peer-Reviewed Original ResearchConceptsAbdominal fat distributionVisceral adipose tissueCIDEA expressionFat distributionProtein levelsAbdominal SATAdolescent girlsHigher visceral adipose tissueSubcutaneous adipose tissue biopsiesAdipose tissue biopsiesReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionMagnetic resonance imagingWeight gain effectsExpression of CIDEAAdipocyte dysfunctionSAT biopsiesAdipose lipidsInsulin resistanceAdipocyte hypertrophySmall adipocytesAdipose tissueTissue biopsiesUnfavorable patternsStrong inverse correlationRacial, ethnic, and gender differences in obesity and body fat distribution: An All of Us Research Program demonstration project
Karnes J, Arora A, Feng J, Steiner H, Sulieman L, Boerwinkle E, Clark C, Cicek M, Cohn E, Gebo K, Loperena-Cortes R, Ohno-Machado L, Mayo K, Mockrin S, Ramirez A, Schully S, Klimentidis Y. Racial, ethnic, and gender differences in obesity and body fat distribution: An All of Us Research Program demonstration project. PLOS ONE 2021, 16: e0255583. PMID: 34358277, PMCID: PMC8345840, DOI: 10.1371/journal.pone.0255583.Peer-Reviewed Original ResearchConceptsBody mass indexBody fat distributionNon-Hispanic blacksNon-Hispanic whitesAlanine aminotransferaseNHB participantsFat distributionAge-adjusted obesity prevalenceNutrition Examination Survey dataBaseline physical examinationRace/ethnicityElectronic health recordsNHB womenWaist circumferenceMass indexHip ratioNHB menPhysical examinationNational HealthObesity prevalenceObesity ratesGender differencesObesityUs Research ProgramNHW participantsChanges in Body Composition, Muscle Strength, and Fat Distribution Following Kidney Transplantation
Dienemann T, Ziolkowski SL, Bender S, Goral S, Long J, Baker JF, Shults J, Zemel BS, Reese PP, Wilson FP, Leonard MB. Changes in Body Composition, Muscle Strength, and Fat Distribution Following Kidney Transplantation. American Journal Of Kidney Diseases 2021, 78: 816-825. PMID: 34352286, PMCID: PMC8608755, DOI: 10.1053/j.ajkd.2020.11.032.Peer-Reviewed Original ResearchConceptsFat mass indexTransplant recipientsMuscle strengthKidney transplantationRelative sarcopeniaZ-scoreMass indexMuscle densityFat massMuscle massAppendicular lean mass indexRace-specific Z-scoresKidney transplant recipientsPrevalence of obesityLongitudinal cohort studyLeg muscle strengthLean mass indexBody composition changesKidney allograftsCohort studyFat distributionHealthy controlsMuscle biopsyPhysical activityTomography measures
2020
Glutamate–Serine–Glycine Index: A Novel Potential Biomarker in Pediatric Non-Alcoholic Fatty Liver Disease
Leonetti S, Herzog RI, Caprio S, Santoro N, Tricò D. Glutamate–Serine–Glycine Index: A Novel Potential Biomarker in Pediatric Non-Alcoholic Fatty Liver Disease. Children 2020, 7: 270. PMID: 33291552, PMCID: PMC7761842, DOI: 10.3390/children7120270.Peer-Reviewed Original ResearchNon-alcoholic fatty liver diseaseAbdominal fat distributionFatty liver diseaseMagnetic resonance imagingGlycine indexLiver diseaseRisk factorsFat distributionPediatric non-alcoholic fatty liver diseasePotential biomarkersIntrahepatic fat accumulationIntrahepatic fat contentTraditional risk factorsRisk pediatric populationsBody mass indexLiver insulin resistanceTwofold higher prevalencePlasma amino acidsNovel potential biomarkersRace/ethnicityNAFLD prevalenceNAFLD patientsMass indexPediatric populationInsulin resistance
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 alterations
2018
A low visceral fat proportion, independent of total body fat mass, protects obese adolescent girls against fatty liver and glucose dysregulation: a longitudinal study
Umano GR, Shabanova V, Pierpont B, Mata M, Nouws J, Tricò D, Galderisi A, Santoro N, Caprio S. A low visceral fat proportion, independent of total body fat mass, protects obese adolescent girls against fatty liver and glucose dysregulation: a longitudinal study. International Journal Of Obesity 2018, 43: 673-682. PMID: 30337653, PMCID: PMC9354568, DOI: 10.1038/s41366-018-0227-6.Peer-Reviewed Original ResearchConceptsBody fat distributionHepatic fat contentGlucose metabolismVisceral fatInsulin resistanceObese adolescentsFat distributionWhole-body insulin sensitivity indexOral glucose tolerance testTotal body fat massSubcutaneous fatIntrahepatic fat contentImpaired glucose metabolismLow ratio groupGlucose tolerance testObese adolescent girlsSubjects/methodsWeBody fat massInsulin sensitivity indexHepatic fat accumulationMajor determinantGlucose dysregulationFatty liverTolerance testFat massPhenomic Impact of Genetically-Determined Euthyroid Function and Molecular Differences between Thyroid Disorders
Ravera S, Carrasco N, Gelernter J, Polimanti R. Phenomic Impact of Genetically-Determined Euthyroid Function and Molecular Differences between Thyroid Disorders. Journal Of Clinical Medicine 2018, 7: 296. PMID: 30248900, PMCID: PMC6210201, DOI: 10.3390/jcm7100296.Peer-Reviewed Original ResearchEuthyroid functionThyroid disordersMolecular differencesExchange factor activityGenome-wide dataMultiple testing correctionConsistent genetic correlationsFree thyroxine levelsTwo-sample Mendelian randomization studyBody fat distributionJAK/STATMendelian randomization studyPhenotypic traitsInter-individual variabilityPotential confoundersFat distributionFemale infertilityMolecular mechanismsThyroxine levelsImmune pathwaysMolecular pathwaysRandomization studyGenetic correlationsHyperthyroidismHypothyroidismAnalysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease
Emdin CA, Khera AV, Chaffin M, Klarin D, Natarajan P, Aragam K, Haas M, Bick A, Zekavat SM, Nomura A, Ardissino D, Wilson JG, Schunkert H, McPherson R, Watkins H, Elosua R, Bown MJ, Samani NJ, Baber U, Erdmann J, Gupta N, Danesh J, Chasman D, Ridker P, Denny J, Bastarache L, Lichtman JH, D’Onofrio G, Mattera J, Spertus JA, Sheu W, Taylor KD, Psaty BM, Rich SS, Post W, Rotter JI, Chen YI, Krumholz H, Saleheen D, Gabriel S, Kathiresan S. Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease. Nature Communications 2018, 9: 1613. PMID: 29691411, PMCID: PMC5915445, DOI: 10.1038/s41467-018-03911-8.Peer-Reviewed Original ResearchConceptsPLOF variantsProtein-coding genetic variantsFunction variantsCoronary artery diseaseBody fat distributionType 2 diabetesEssential splice siteProtein functionEffector transcriptsUK Biobank participantsIdentifies variantsStop codonMetabolic traitsArtery diseaseSplice siteAllergic diseasesAssociation analysisCardiometabolic diseasesAdditional diseaseFat distributionGenetic variantsBiobank participantsDiseaseBiological effectsVariants
2017
Correlations of Abdominal Fat and Colonic Sulfidogenic Bacteria in African Americans and Non‐Hispanic Whites with Newly Diagnosed Colorectal Cancer
Gomez‐Perez S, Yazici C, Wolf P, Braunschweig C, Xicola R, Llor X, Ellis N, Tussing‐Humphreys L, Mutlu E, Gaskins R. Correlations of Abdominal Fat and Colonic Sulfidogenic Bacteria in African Americans and Non‐Hispanic Whites with Newly Diagnosed Colorectal Cancer. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.138.7.Peer-Reviewed Original ResearchAbdominal fat distributionNon-Hispanic whitesNational Cancer InstituteColonic mucosaAbdominal fatWaist circumferenceColorectal cancerCancer InstitutePreoperative abdominal computed tomography scansAfrican AmericansAbdominal computed tomography scanIncident colorectal cancerComputed tomography scanGene targetsIncident CRCMean ageFat distributionTomography scanColonic tissueGut microbiotaAbundance of DesulfovibrioL3 vertebraMucosaSignificant correlationCancer
2016
The Adipose Tissue Microenvironment Regulates Depot-Specific Adipogenesis in Obesity
Jeffery E, Wing A, Holtrup B, Sebo Z, Kaplan JL, Saavedra-Peña R, Church CD, Colman L, Berry R, Rodeheffer MS. The Adipose Tissue Microenvironment Regulates Depot-Specific Adipogenesis in Obesity. Cell Metabolism 2016, 24: 142-150. PMID: 27320063, PMCID: PMC4945385, DOI: 10.1016/j.cmet.2016.05.012.Peer-Reviewed Original ResearchConceptsVisceral white adipose tissueHigh-fat dietAdipose tissueAdipocyte precursorsAdipocyte hyperplasiaDepot-specific adipogenesisDifferential fat distributionObesity-associated pathologiesWhite adipose tissueAdipose tissue microenvironmentSubcutaneous adipose tissueAdipose tissue growthCell-intrinsic mechanismsMetabolic healthFat distributionMale miceHormone-dependent mannerDimorphic distributionObesityHyperplasiaAdipogenesisTissue microenvironmentTissueMicroenvironmentPlastic cells
2015
Abdominal fat radiodensity, quantity and cardiometabolic risk: The Multi-Ethnic Study of Atherosclerosis
Shah R, Allison M, Lima J, Abbasi S, Eisman A, Lai C, Jerosch-Herold M, Budoff M, Murthy V. Abdominal fat radiodensity, quantity and cardiometabolic risk: The Multi-Ethnic Study of Atherosclerosis. Nutrition Metabolism And Cardiovascular Diseases 2015, 26: 114-122. PMID: 26817938, PMCID: PMC4775418, DOI: 10.1016/j.numecd.2015.12.002.Peer-Reviewed Original ResearchMeSH KeywordsAbdominal FatAdiponectinAdiposityAgedAtherosclerosisBiomarkersC-Reactive ProteinFemaleHumansIncidenceInsulinIntra-Abdominal FatLeptinLinear ModelsLogistic ModelsMaleMetabolic SyndromeMiddle AgedMultivariate AnalysisOdds RatioPredictive Value of TestsPrevalenceProportional Hazards ModelsRisk FactorsSubcutaneous Fat, AbdominalTomography, X-Ray ComputedUnited StatesConceptsCardiometabolic riskAssociated with prevalent MetSCardiovascular disease risk factorsMulti-Ethnic Study of AtherosclerosisMeasures of regional fat distributionAssociated with incident MetSMarkers of cardiometabolic riskIncident metabolic syndromeDisease risk factorsFat radiodensityMetabolic syndromeMulti-Ethnic StudyStudy of AtherosclerosisVisceral fat quantityIncident MetSPrevalent MetSRegional fat distributionComputed tomographyMeasure associationsFat quantityFat distributionRisk factorsCardiometabolic dysfunctionAssociated with quantityIntermuscular fat depots
2012
Impact of Obesity and Body Fat Distribution on Survival After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma
Gaujoux S, Torres J, Olson S, Winston C, Gonen M, Brennan M, Klimstra D, D’Angelica M, DeMatteo R, Fong Y, House M, Jarnagin W, Kurtz R, Allen P. Impact of Obesity and Body Fat Distribution on Survival After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma. Annals Of Surgical Oncology 2012, 19: 2908-2916. PMID: 22411205, DOI: 10.1245/s10434-012-2301-y.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedBlood Loss, SurgicalBody Fat DistributionBody Mass IndexDisease-Free SurvivalFemaleHumansIntra-Abdominal FatKaplan-Meier EstimateMaleMiddle AgedObesityOperative TimePancreatic NeoplasmsPancreaticoduodenectomyProportional Hazards ModelsStatistics, NonparametricSurvival RateConceptsVisceral fat areaBody fat distributionBody mass indexBody mass index classTumor characteristicsFat distributionCancer-related outcomesPancreatic adenocarcinomaPathological characteristicsClinical relevance of obesityVisceral fat area quartilesVisceral fat area valuesSignificantly higher blood lossInfluence of body mass indexDisease-free survivalPancreatic cancer riskPancreatic fatty infiltrationRelevance of obesityHigher blood lossInfluence of obesityImpact of obesityPancreatic ductal adenocarcinomaResultsA significant positive correlationIncreased body weightBlood loss
2011
Relationship between sleep apnea, fat distribution, and insulin resistance in obese children.
Canapari CA, Hoppin AG, Kinane TB, Thomas BJ, Torriani M, Katz ES. Relationship between sleep apnea, fat distribution, and insulin resistance in obese children. Journal Of Clinical Sleep Medicine 2011, 7: 268-73. PMID: 21677896, PMCID: PMC3113965, DOI: 10.5664/jcsm.1068.Peer-Reviewed Original ResearchConceptsObstructive sleep apneaHomeostasis model assessmentBody mass indexLog homeostasis model assessmentBMI z-scoreObese childrenInsulin resistanceFat distributionSleep apneaMean body mass indexSubcutaneous adipose tissue areaZ-scoreVisceral fat areaVisceral fat distributionSubset of patientsAdipose tissue areaPediatric obesity clinicSubset of subjectsMagnetic resonance imagingOSA pathogenesisObesity clinicOSA severityObese subjectsMass indexFat area
2009
Glucose dysregulation and hepatic steatosis in obese adolescents: Is there a link?
Cali AM, De Oliveira AM, Kim H, Chen S, Reyes‐Mugica M, Escalera S, Dziura J, Taksali SE, Kursawe R, Shaw M, Savoye M, Pierpont B, Constable RT, Caprio S. Glucose dysregulation and hepatic steatosis in obese adolescents: Is there a link? Hepatology 2009, 49: 1896-1903. PMID: 19434725, PMCID: PMC2692562, DOI: 10.1002/hep.22858.Peer-Reviewed Original ResearchConceptsHepatic fat fractionObese adolescentsHepatic fat contentGlucose dysregulationHepatic steatosisMetabolic syndromeFatty liverInsulin sensitivityTotal fatHigher hepatic fat fractionStandard oral glucose tolerance testOral glucose tolerance testTwo-hour plasma glucoseSubcutaneous fat ratioHomeostasis model assessmentAbdominal fat distributionGlucose tolerance testProinflammatory milieuHMW adiponectinIL-6Insulin resistanceMatsuda indexTolerance testPlasma glucoseFat distribution
2007
Interethnic Differences in Muscle, Liver and Abdominal Fat Partitioning in Obese Adolescents
Liska D, Dufour S, Zern TL, Taksali S, Calí AM, Dziura J, Shulman GI, Pierpont BM, Caprio S. Interethnic Differences in Muscle, Liver and Abdominal Fat Partitioning in Obese Adolescents. PLOS ONE 2007, 2: e569. PMID: 17593968, PMCID: PMC1892806, DOI: 10.1371/journal.pone.0000569.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingLiver fat contentHepatic fat contentInsulin resistanceObese adolescentsAfrican AmericansOral glucose tolerance testingObese Hispanic adolescentsAbdominal fat distributionGlucose tolerance testingType 2 diabetesTotal body fatEthnic differencesClear ethnic differencesVisceral fatInsulin sensitivityFat distributionTolerance testingIMCL levelsMultiethnic cohortObese youthFat contentAbdominal cavityBody fatSoleus muscle
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