2023
Incretin effect determines glucose trajectory and insulin sensitivity in youths with obesity
Galderisi A, Tricò D, Lat J, Samuels S, Weiss R, Van Name M, Pierpont B, Santoro N, Caprio S. Incretin effect determines glucose trajectory and insulin sensitivity in youths with obesity. JCI Insight 2023, 8: e165709. PMID: 37847560, PMCID: PMC10721315, DOI: 10.1172/jci.insight.165709.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testΒ-cell functionIncretin effectBeta-cell functionInsulin sensitivityInsulin secretionGlucose levelsCell functionIsoglycemic intravenous glucose infusionGreater insulin sensitivityIntravenous glucose infusionPubertal transitionGlucose tolerance testGLP-17Glucagon suppressionGlucose infusionObesityLongitudinal increaseBaselineOGTTEffect groupGreater increaseLongitudinal trajectoriesSecretionGroupHigh-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities
Bloyd M, Sinaii N, Faucz F, Iben J, Coon S, Caprio S, Santoro N, Stratakis C, London E. High-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities. Frontiers In Endocrinology 2023, 14: 1272939. PMID: 38027204, PMCID: PMC10679389, DOI: 10.3389/fendo.2023.1272939.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSignaling-related genesProtein kinaseHigh-frequency variantsCAMP-dependent protein kinaseLarge-scale genome-wide association studiesNew genetic associationsPDE11A geneGenomic DNAAssociation studiesMonogenic obesityTargeted exome sequencingGenesGenetic variantsEnergy metabolismGenetic associationExome sequencingNovel variantsVariant searchMetabolic characteristicsVariantsKinaseType II diabetesLociSequencingThe lncOb rs10487505 polymorphism impairs insulin sensitivity and glucose tolerance in children and adolescents with obesity
Umano G, Cirillo G, Sanchez G, Rondinelli G, Foderini M, Ferrara S, Di Sessa A, Marzuillo P, Papparella A, Santoro N, del Giudice E. The lncOb rs10487505 polymorphism impairs insulin sensitivity and glucose tolerance in children and adolescents with obesity. Obesity 2023, 31: 2359-2364. PMID: 37550829, DOI: 10.1002/oby.23835.Peer-Reviewed Original ResearchConceptsHomeostasis model assessmentInsulin resistanceDisposition indexLower whole-body insulin sensitivity indexModel assessmentWhole-body insulin sensitivity indexRisk of prediabetesHigher fasting insulinLower disposition indexPlasma leptin levelsInsulin sensitivity indexBMI z-scoreLeptin plasma levelsLeptin gene transcriptionFasting insulinGlucose toleranceLeptin levelsCC patientsRetrospective studyPlasma levelsAnthropometrical evaluationInsulin sensitivityHormone levelsHigh prevalenceHigh riskProatherogenic changes in lipoprotein particles associated with a high triglyceride to high‐density lipoprotein cholesterol ratio in youths
Chiriacò M, Nesti L, Natali A, Santoro N, Caprio S, Tricò D. Proatherogenic changes in lipoprotein particles associated with a high triglyceride to high‐density lipoprotein cholesterol ratio in youths. Obesity 2023, 31: 1894-1902. PMID: 37227148, PMCID: PMC10330115, DOI: 10.1002/oby.23767.Peer-Reviewed Original ResearchConceptsTG/HDL ratioHigh TG/HDL ratioHigh-density lipoprotein cholesterol ratioLipoprotein cholesterol ratioHDL ratioLow-density lipoproteinHigh triglyceridesCholesterol ratioLipoprotein subclassesElevated TG/HDL ratioOral glucose tolerance testAbdominal magnetic resonance imagingIncreased cardiovascular riskTG/HDLOverweight/obesityGlucose tolerance testLipoprotein particle concentrationsIntermediate density lipoproteinPlasma lipoprotein subclassesMagnetic resonance imagingRace/ethnicityProatherogenic changesCardiovascular eventsCardiovascular riskSmall LDLComparison of Metabolic Response to Colonic Fermentation in Lean Youth vs Youth With Obesity
Galuppo B, Umano G, Li Z, Van Name M, Samuels S, Kien C, Cline G, Wagner D, Barbieri E, Tricò D, Santoro N. Comparison of Metabolic Response to Colonic Fermentation in Lean Youth vs Youth With Obesity. JAMA Network Open 2023, 6: e2312530. PMID: 37159195, PMCID: PMC10170343, DOI: 10.1001/jamanetworkopen.2023.12530.Peer-Reviewed Original ResearchConceptsInsulin sensitivity indexCross-sectional studyFree fatty acidsColonic fermentationActive glucagon-like peptide-1Plasma free fatty acidsGlucagon-like peptide-1Indigestible dietary carbohydratesReduction of ghrelinActive GLP-1Health care burdenBody mass indexMetabolic responseInsulin-resistant groupLean youthObese insulinOIS groupPYY responseAnorexigenic responsePediatric obesityMass indexTyrosine tyrosineInsulin resistanceIntravenous infusionHormone secretionStudy protocol for a randomized, controlled trial using a novel, family-centered diet treatment to prevent NAFLD in Hispanic children
Welsh J, Pyo E, Huneault H, Ramirez L, Alazraki A, Alli R, Dunbar S, Khanna G, Knight-Scott J, Pimentel A, Reed B, Rodney-Somersall C, Santoro N, Umpierrez G, Vos M. Study protocol for a randomized, controlled trial using a novel, family-centered diet treatment to prevent NAFLD in Hispanic children. Contemporary Clinical Trials 2023, 129: 107170. PMID: 37019180, PMCID: PMC10734403, DOI: 10.1016/j.cct.2023.107170.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseHispanic childrenFuture dietary guidelinesFatty liver diseasePrimary study outcomeLiver fat accumulationHigh-risk childrenSignificant hepatic steatosisOne-year interventionPercentile BMIElevated liverSecondary outcomesNAFLD preventionLiver diseaseLiver steatosisNAFLD pathogenesisPrevious diagnosisHepatic fatHepatic steatosisStudy protocolDietary guidelinesFat accumulationLiver disordersMetabolic markersEligibility criteriaClinical features and metabolic complications for non-alcoholic fatty liver disease (NAFLD) in youth with obesity
Barbieri E, Santoro N, Umano G. Clinical features and metabolic complications for non-alcoholic fatty liver disease (NAFLD) in youth with obesity. Frontiers In Endocrinology 2023, 14: 1062341. PMID: 36733529, PMCID: PMC9887046, DOI: 10.3389/fendo.2023.1062341.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseInsulin resistancePediatric obesityDevelopment of NAFLDWhole-body insulin resistanceFatty liver diseaseType 2 diabetesAdipose tissue lipolysisCommon metabolic diseaseMetabolic complicationsClinical featuresLiver diseasePediatric populationTherapeutic optionsEctopic tissuePathophysiologic underpinningsTissue lipolysisRole of geneticsMetabolic diseasesObesityControl of insulinGrowth hormoneClinical implicationsDiseaseFatty acids
2020
rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis
Teo K, Abeysekera KWM, Adams L, Aigner E, Anstee QM, Banales JM, Banerjee R, Basu P, Berg T, Bhatnagar P, Buch S, Canbay A, Caprio S, Chatterjee A, Chen Y, Chowdhury A, Daly AK, Datz C, de Gracia Hahn D, DiStefano JK, Dong J, Duret A, Investigators E, Vreugdenhil A, Alisi A, Socha P, Jańczyk W, Baumann U, Rajwal S, van Mourik I, Lacaille F, Dabbas M, Kelly D, Nobili V, Emdin C, Fairey M, Gerhard G, Consortium G, Eiriksdottir G, Garcia M, Gudnason V, Harris T, Kim L, Launer L, Nalls M, Smith A, Clark J, Hernaez R, Kao W, Mitchell B, Shuldiner A, Yerges-Armstrong L, Borecki I, Carr J, Feitosa M, Wu J, Butler J, Fox C, Hirschhorn J, Hoffmann U, Hwang S, Massaro J, O'Donnell C, Palmer C, Sahani D, Speliotes E, Guo X, Hampe J, Hickman M, Heintz L, Hudert C, Hunter H, Kelly M, Kozlitina J, Krawczyk M, Lammert F, Langenberg C, Lavine J, Li L, Lim H, Loomba R, Luukkonen P, Melton P, Mori T, Palmer N, Parisinos C, Pillai S, Qayyum F, Reichert M, Romeo S, Rotter J, Im Y, Santoro N, Schafmayer C, Speliotes E, Stender S, Stickel F, Still C, Strnad P, Taylor K, Tybjærg-Hansen A, Umano G, Utukuri M, Valenti L, Wagenknecht L, Wareham N, Watanabe R, Wattacheril J, Yaghootkar H, Yki-Järvinen H, Young K, Mann J. rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis. Journal Of Hepatology 2020, 74: 20-30. PMID: 32882372, PMCID: PMC7755037, DOI: 10.1016/j.jhep.2020.08.027.Peer-Reviewed Original ResearchConceptsFatty liver diseaseLiver diseaseAlanine aminotransferaseLiver fatRisk factorsSevere fatty liver diseaseCaucasian adultsHigh liver fatSpectrum of NAFLDDiagnosis of NAFLDSerum alanine aminotransferaseSeverity of NAFLDLower serum triglyceridesHigher alanine aminotransferaseCT/MRIDominant genetic modelRelated metabolic phenotypesGenome-wide association studiesPopulation-level dataNAFLD histologyAdvanced fibrosisLiver inflammationSerum triglyceridesHepatic fatAdvanced histologyEffect of Gut Microbiota and PNPLA3 rs738409 Variant on Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Youth
Kravetz A, Testerman T, Galuppo B, Graf J, Pierpont B, Siebel S, Feinn R, Santoro N. Effect of Gut Microbiota and PNPLA3 rs738409 Variant on Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Youth. The Journal Of Clinical Endocrinology & Metabolism 2020, 105: dgaa382. PMID: 32561908, PMCID: PMC7458486, DOI: 10.1210/clinem/dgaa382.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseHepatic fat fractionFatty liver diseasePNPLA3 rs738409Obese youthLiver diseaseGut microbiotaDifferent gut microbiota compositionNonalcoholic fatty liver diseaseOral glucose tolerance testPNPLA3 rs738409 variantPediatric obesity clinicGlucose tolerance testCross-sectional studyGut microbiota compositionAbdominal magnetic resonanceNAFLD statusRs738409 variantObesity clinicPNPLA3 genotypeObese childrenTolerance testBacteroidetes ratioCommon causeRs738409
2019
Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls
Flannick J, Mercader JM, Fuchsberger C, Udler MS, Mahajan A, Wessel J, Teslovich TM, Caulkins L, Koesterer R, Barajas-Olmos F, Blackwell TW, Boerwinkle E, Brody JA, Centeno-Cruz F, Chen L, Chen S, Contreras-Cubas C, Córdova E, Correa A, Cortes M, DeFronzo RA, Dolan L, Drews KL, Elliott A, Floyd JS, Gabriel S, Garay-Sevilla ME, García-Ortiz H, Gross M, Han S, Heard-Costa NL, Jackson AU, Jørgensen ME, Kang HM, Kelsey M, Kim BJ, Koistinen HA, Kuusisto J, Leader JB, Linneberg A, Liu CT, Liu J, Lyssenko V, Manning AK, Marcketta A, Malacara-Hernandez JM, Martínez-Hernández A, Matsuo K, Mayer-Davis E, Mendoza-Caamal E, Mohlke KL, Morrison AC, Ndungu A, Ng MCY, O’Dushlaine C, Payne AJ, Pihoker C, Post W, Preuss M, Psaty B, Vasan R, Rayner N, Reiner A, Revilla-Monsalve C, Robertson N, Santoro N, Schurmann C, So W, Soberón X, Stringham H, Strom T, Tam C, Thameem F, Tomlinson B, Torres J, Tracy R, van Dam R, Vujkovic M, Wang S, Welch R, Witte D, Wong T, Atzmon G, Barzilai N, Blangero J, Bonnycastle L, Bowden D, Chambers J, Chan E, Cheng C, Cho Y, Collins F, de Vries P, Duggirala R, Glaser B, Gonzalez C, Gonzalez M, Groop L, Kooner J, Kwak S, Laakso M, Lehman D, Nilsson P, Spector T, Tai E, Tuomi T, Tuomilehto J, Wilson J, Aguilar-Salinas C, Bottinger E, Burke B, Carey D, Chan J, Dupuis J, Frossard P, Heckbert S, Hwang M, Kim Y, Kirchner H, Lee J, Lee J, Loos R, Ma R, Morris A, O’Donnell C, Palmer C, Pankow J, Park K, Rasheed A, Saleheen D, Sim X, Small K, Teo Y, Haiman C, Hanis C, Henderson B, Orozco L, Tusié-Luna T, Dewey F, Baras A, Gieger C, Meitinger T, Strauch K, Lange L, Grarup N, Hansen T, Pedersen O, Zeitler P, Dabelea D, Abecasis G, Bell G, Cox N, Seielstad M, Sladek R, Meigs J, Rich S, Rotter J, Altshuler D, Burtt N, Scott L, Morris A, Florez J, McCarthy M, Boehnke M. Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls. Nature 2019, 570: 71-76. PMID: 31118516, PMCID: PMC6699738, DOI: 10.1038/s41586-019-1231-2.Peer-Reviewed Original ResearchConceptsExome-wide significanceProtein-coding genetic variantsDrug targetsRare variantsGene-level associationsType 2 diabetesRare variant associationsGene setsCandidate genesExome sequencing analysisGenetic variantsNon-diabetic control participantsExome sequencingGenesKnockout micePrioritization effortsDisease riskVariantsFuture targetsControl participantsTargetDiabetesEffect sizeSequencingHeritability
2018
Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort
Tricò D, Caprio S, Umano G, Pierpont B, Nouws J, Galderisi A, Kim G, Mata MM, Santoro N. Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort. Hepatology 2018, 68: 1376-1390. PMID: 29665034, PMCID: PMC6173637, DOI: 10.1002/hep.30035.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdolescentBiopsy, NeedleBody Mass IndexCross-Sectional StudiesFemaleGene Expression RegulationGlucose Tolerance TestHumansImmunohistochemistryInsulin ResistanceMagnetic Resonance ImagingMaleMembrane ProteinsNon-alcoholic Fatty Liver DiseasePediatric ObesityPolymerase Chain ReactionPolymorphism, Single NucleotidePrognosisProspective StudiesROC CurveConceptsNonalcoholic fatty liverNonalcoholic fatty liver diseaseOral glucose tolerance testHepatic fat fractionObese adolescentsFatty liverMagnetic resonance imagingLiver diseaseMultiethnic cohortAbdominal magnetic resonance imagingC-peptide levelsChronic liver diseaseFatty liver diseaseGlucose tolerance testSingle nucleotide polymorphismsAltered glucose homeostasisGlucose toleranceLiver steatosisProspective studyInsulin resistanceTolerance testInsulin sensitivityRisk factorsCommon causeHigh prevalenceThe rs626283 Variant in the MBOAT7 Gene is Associated with Insulin Resistance and Fatty Liver in Caucasian Obese Youth
Umano GR, Caprio S, Di Sessa A, Chalasani N, Dykas DJ, Pierpont B, Bale AE, Santoro N. The rs626283 Variant in the MBOAT7 Gene is Associated with Insulin Resistance and Fatty Liver in Caucasian Obese Youth. The American Journal Of Gastroenterology 2018, 113: 376. PMID: 29485130, DOI: 10.1038/ajg.2018.1.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAdolescentAllelesBlack or African AmericanChildFemaleGenetic Predisposition to DiseaseGenotypeGlucose Tolerance TestHispanic or LatinoHumansInsulin ResistanceLiverMagnetic Resonance ImagingMaleMembrane ProteinsNon-alcoholic Fatty Liver DiseasePediatric ObesityPolymorphism, Single NucleotideWhite PeopleConceptsCaucasian obese childrenMBOAT7 geneObese childrenLiver diseaseHepatic steatosisInsulin resistanceInsulin sensitivityAlcoholic fatty liver diseaseBody mass index z-scoreOral glucose tolerance testWhole-body insulin sensitivityAlcoholic liver diseaseFatty liver diseaseCurve of glucoseGlucose tolerance testIndex z-scoreMagnetic resonance imagingFatty liverPNPLA3 rs738409Liver damageTolerance testLeading causeMultiethnic cohortObese youthGlucose metabolism
2017
Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota?
Tricò D, Di Sessa A, Caprio S, Chalasani N, Liu W, Liang T, Graf J, Herzog R, Johnson CD, Umano GR, Feldstein AE, Santoro N. Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota? Antioxidants & Redox Signaling 2017, 30: 241-250. PMID: 28279074, PMCID: PMC6277079, DOI: 10.1089/ars.2017.7049.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAge FactorsBiomarkersChildDelta-5 Fatty Acid DesaturaseDisease SusceptibilityFatty Acid DesaturasesFemaleGastrointestinal MicrobiomeGenetic BackgroundGenetic Predisposition to DiseaseHaplotypesHumansLinoleic AcidLipid MetabolismLipoproteinsMaleMetabolic SyndromeMetabolomeObesityOxidation-ReductionConceptsProatherogenic lipoprotein profilePediatric metabolic syndromeLipoprotein profileGut microbiotaGut bacterial loadMetabolic syndromeObese adolescentsSmall dense low-density lipoproteinBacterial loadAdverse lipoprotein profileLow-density lipoprotein particlesHigher plasma concentrationsLow-density lipoproteinLinoleic acid metabolitesPlasma 9Haplotype AAPathogenic rolePlasma concentrationsGenetic predispositionAcid metabolitesGenetic backgroundLipoprotein particlesMetSSyndromeMicrobiota
2016
Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: A multiethnic study
Goffredo M, Caprio S, Feldstein AE, D'Adamo E, Shaw MM, Pierpont B, Savoye M, Zhao H, Bale AE, Santoro N. Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: A multiethnic study. Hepatology 2016, 63: 117-125. PMID: 26457389, PMCID: PMC4688225, DOI: 10.1002/hep.28283.Peer-Reviewed Original ResearchConceptsFatty liver diseaseHepatic fat contentLiver diseaseLiver biopsyTM6SF2 rs58542926Nonalcoholic fatty liver disease activity scorePediatric nonalcoholic fatty liver diseaseHigh hepatic fat contentPediatric fatty liver diseaseHigher alanine aminotransferase levelsNonalcoholic fatty liver diseaseOral glucose tolerance testMinor alleleDisease Activity ScoreIntrahepatic fat accumulationUnderwent liver biopsyAlanine aminotransferase levelsFavorable lipoprotein profileGlucose tolerance testLiver panelAminotransferase levelsCardiovascular riskActivity scoreObese childrenLipoprotein profile
2015
A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents
Kursawe R, Dixit VD, Scherer PE, Santoro N, Narayan D, Gordillo R, Giannini C, Lopez X, Pierpont B, Nouws J, Shulman GI, Caprio S. A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents. Diabetes 2015, 65: 610-618. PMID: 26718495, PMCID: PMC4764142, DOI: 10.2337/db15-1478.Peer-Reviewed Original ResearchMeSH KeywordsAbdomenAcetyl-CoA CarboxylaseAdipogenesisAdiponectinAdolescentCarrier ProteinsCaspase 1ChildDown-RegulationFatty Acid Synthase, Type IFemaleGene Expression ProfilingGlucose Transporter Type 4HumansInflammasomesInsulin ResistanceInterleukin-1betaIntra-Abdominal FatLeptinLipogenesisLipoprotein LipaseMacrophagesMagnetic Resonance ImagingMaleNLR Family, Pyrin Domain-Containing 3 ProteinObesityPPAR gammaSirtuin 1Sterol Regulatory Element Binding Protein 1Subcutaneous FatToll-Like Receptor 4ConceptsVisceral adipose tissueObese adolescentsInsulin resistanceTissue inflammationNLRP3 inflammasomeAdipose tissueInnate immune cell sensorsAbdominal subcutaneous adipose tissueAbdominal adipose depotsAbdominal fat partitioningAdipogenesis/lipogenesisAdipose tissue inflammationProinflammatory cytokines interleukinInfiltration of macrophagesExpression of CASP1Subcutaneous adipose tissueInflammation markersSAT biopsiesIL-18Macrophage infiltrationVisceral fatCytokines interleukinSAT ratioInsulin sensitivityAdipose depots
2006
Growth acceleration in prepubertal obese children: role of hyperinsulinaemia.
Santoro N, Miraglia Del Giudice E, Coppola F, Luongo C, Perrone L. Growth acceleration in prepubertal obese children: role of hyperinsulinaemia. Acta Paediatrica 2006, 95: 887-8. PMID: 16801195, DOI: 10.1080/08035250600580560.Peer-Reviewed Original Research
2001
Mutational Screening of the CART Gene in Obese Children Identifying a Mutation (Leu34Phe) Associated With Reduced Resting Energy Expenditure and Cosegregating With Obesity Phenotype in a Large Family
del Giudice E, Santoro N, Cirillo G, D’Urso L, Di Toro R, Perrone L. Mutational Screening of the CART Gene in Obese Children Identifying a Mutation (Leu34Phe) Associated With Reduced Resting Energy Expenditure and Cosegregating With Obesity Phenotype in a Large Family. Diabetes 2001, 50: 2157-2160. PMID: 11522684, DOI: 10.2337/diabetes.50.9.2157.Peer-Reviewed Original ResearchConceptsObesity onsetObesity phenotypesEnergy expenditureZ-scoreObese Italian childrenSevere obesity phenotypeBMI z-scoreAmphetamine-regulated transcriptResting Energy ExpenditureCART geneCodon 34CART effectsSympathetic outflowObese patientsLeptin levelsObese childrenObese subjectsHypothalamic areaBMI percentileAppetite regulationCART peptideObese boysAverage agePatientsControl population