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 distribution
2022
978-P: Rare Variants in Melanocortin 4 Receptor Gene (MC4R) Are Associated with Increased Visceral Fat and Altered Glucose Metabolism Independent of the Effect of Obesity in Children
GALUPPO B, MANNAM P, TRICO D, BALE A, CAPRIO S, SANTORO N. 978-P: Rare Variants in Melanocortin 4 Receptor Gene (MC4R) Are Associated with Increased Visceral Fat and Altered Glucose Metabolism Independent of the Effect of Obesity in Children. Diabetes 2022, 71 DOI: 10.2337/db22-978-p.Peer-Reviewed Original ResearchOral glucose tolerance testEffect of obesityIntrahepatic fatInsulin resistanceVisceral fatMelanocortin-4 receptor gene mutationsVariant groupsSimilar BMI z-scoresOverweight/obese youthRare variantsAbdominal fat distributionGlucose tolerance testLower insulin clearanceBMI z-scoreEarly-onset obesityBody fat percentageΒ-cell functionGreater visceral fatMelanocortin-4 receptor geneHigher plasma glucoseRegion of MC4RReceptor gene mutationsMetabolic sequelaeInsulin clearanceTolerance test
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 correlation
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
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
2010
Central Role of Fatty Liver in the Pathogenesis of Insulin Resistance in Obese Adolescents
D'Adamo E, Cali AM, Weiss R, Santoro N, Pierpont B, Northrup V, Caprio S. Central Role of Fatty Liver in the Pathogenesis of Insulin Resistance in Obese Adolescents. Diabetes Care 2010, 33: 1817-1822. PMID: 20668154, PMCID: PMC2909068, DOI: 10.2337/dc10-0284.Peer-Reviewed Original ResearchConceptsObese adolescentsFatty liverHFF groupVisceral fatLower whole-body insulin sensitivity indexTwo-step hyperinsulinemic-euglycemic clampWhole-body insulin sensitivity indexOral glucose tolerance testBaseline fatty acidsHepatic glucose production rateLow-dose insulinAbdominal fat distributionGlucose disposal rateIntramyocellular lipid contentGlucose tolerance testBeta-cell functionHyperinsulinemic-euglycemic clampInsulin sensitivity indexBMI z-scoreHepatic fat contentInsulin-resistant statesMagnetic resonance imagingSuppression of EGPGlucose production rateInsulin resistance
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
2003
Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning
Weiss R, Dufour S, Taksali SE, Tamborlane WV, Petersen KF, Bonadonna RC, Boselli L, Barbetta G, Allen K, Rife F, Savoye M, Dziura J, Sherwin R, Shulman GI, Caprio S. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning. The Lancet 2003, 362: 951-957. PMID: 14511928, PMCID: PMC2995523, DOI: 10.1016/s0140-6736(03)14364-4.Peer-Reviewed Original ResearchConceptsImpaired glucose toleranceNormal glucose toleranceGlucose toleranceObese childrenInsulin resistanceObese adolescentsGlucose disposalInsulin sensitivitySevere peripheral insulin resistanceNon-oxidative glucose metabolismSubcutaneous fatH plasma glucose concentrationsAbdominal fat partitioningVisceral lipid contentsPeripheral glucose disposalHigher intramyocellular lipid contentAbdominal fat distributionDegree of obesityIntramyocellular lipid contentPeripheral insulin resistanceHigh visceral fatAbdominal subcutaneous fatEuglycaemic hyperinsulinaemic clampSevere insulin resistancePlasma glucose concentrationLow Adiponectin Levels in Adolescent Obesity: A Marker of Increased Intramyocellular Lipid Accumulation
Weiss R, Dufour S, Groszmann A, Petersen K, Dziura J, Taksali SE, Shulman G, Caprio S. Low Adiponectin Levels in Adolescent Obesity: A Marker of Increased Intramyocellular Lipid Accumulation. The Journal Of Clinical Endocrinology & Metabolism 2003, 88: 2014-2018. PMID: 12727947, DOI: 10.1210/jc.2002-021711.Peer-Reviewed Original ResearchConceptsAdiponectin levelsInsulin sensitivityAdolescent obesityObese adolescentsPutative modulatory effectsLower adiponectin levelsAbdominal fat distributionIntramyocellular lipid contentPlasma adiponectin levelsIntramyocellular lipid accumulationEuglycemic hyperinsulinemic clampTotal body fatMagnetic resonance imagingCentral adiposityPediatric populationInsulin resistanceIntramuscular lipid contentTriglyceride levelsFat distributionLipid contentPlasma triglyceridesFree fatty acidsBody fatModulatory effectsAdiponectin
1994
Stress‐Induced Cortisol Response and Fat Distribution in Women
Moyer A, Rodin J, Grilo C, Cummings N, Larson L, Rebuffé‐Scrive M. Stress‐Induced Cortisol Response and Fat Distribution in Women. Obesity 1994, 2: 255-262. PMID: 16353426, DOI: 10.1002/j.1550-8528.1994.tb00055.x.Peer-Reviewed Original ResearchConceptsAbdominal fat distributionFat distributionCortisol secretionUncontrollable stressAdrenal cortical systemBody fat distributionStressful sessionStress-induced cortisol responsesSalivary cortisol levelsMinutes of stressControl rest sessionOverweight womenHip ratioHigh WHRCortisol responseCortisol levelsRest sessionObserved associationsLaboratory stressorLife stressSecretionMood reactivityRest daysCortisolPsychological trait variables
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