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
Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™‐1 and ‐2)
Wharton S, le Roux C, Kosiborod M, Platz E, Brueckmann M, Jastreboff A, Hussain S, Pedersen S, Borowska L, Unseld A, Kloer I, Kaplan L, committees and investigators T. Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™‐1 and ‐2). Obesity 2024, 33: 67-77. PMID: 39495965, PMCID: PMC11664303, DOI: 10.1002/oby.24184.Peer-Reviewed Original ResearchTreatment of obesityBaseline BMIRandomized phase 3 clinical trialOnce-weekly subcutaneous injectionsPhase 3 clinical trialsBaseline to weekDouble-blind trialObesity-related complicationsBody weight reductionAbsence of T2DSystolic blood pressureLiver fat contentType 2 diabetesMagnetic resonance imagingMeasures of glycemiaSecondary endpointsDosing flexibilityProportion of participantsLifestyle modificationInvestigated glucagonSubcutaneous injectionBlood pressureBody compositionResonance imagingObesityAltered 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
191-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 mice
2021
319-OR: Effects of Empagliflozin on Markers of Liver Steatosis and Fibrosis and Their Relation to Cardiorenal Outcomes in the EMPA-REG OUTCOME Trial
KAHL S, OFSTAD A, ZINMAN B, WANNER C, SCHUELER E, INZUCCHI S, RODEN M. 319-OR: Effects of Empagliflozin on Markers of Liver Steatosis and Fibrosis and Their Relation to Cardiorenal Outcomes in the EMPA-REG OUTCOME Trial. Diabetes 2021, 70 DOI: 10.2337/db21-319-or.Peer-Reviewed Original ResearchNonalcoholic fatty liver diseaseNAFLD fibrosis scoreCardiorenal outcomesFibrosis riskEMPA-REG OUTCOMELiver fat contentRisk of steatosisEffect of empagliflozinFatty liver diseaseType 2 diabetesCause deathDaily empagliflozinSteatosis indexHeart failureFibrosis scoreLiver diseaseCox regressionCardiovascular diseaseHigh riskEmpagliflozinPlaceboSteatosisRisk categoriesBaselineMeasures analysis
2012
Hepatic Fat Accumulation Is Modulated by the Interaction between the rs738409 Variant in the PNPLA3 Gene and the Dietary Omega6/Omega3 PUFA Intake
Santoro N, Savoye M, Kim G, Marotto K, Shaw MM, Pierpont B, Caprio S. Hepatic Fat Accumulation Is Modulated by the Interaction between the rs738409 Variant in the PNPLA3 Gene and the Dietary Omega6/Omega3 PUFA Intake. PLOS ONE 2012, 7: e37827. PMID: 22629460, PMCID: PMC3357343, DOI: 10.1371/journal.pone.0037827.Peer-Reviewed Original ResearchConceptsALT levelsObese youthSingle nucleotide polymorphismsRs738409 single nucleotide polymorphismFatty acid intakeFatty liver developmentLiver fat contentHepatic fat accumulationNutrition Data SystemRs738409 variantPNPLA3 genotypePUFA intakeFatty liverAcid intakeHepatic steatosisHepatic fatLiver damageDietary factorsFat accumulationPNPLA3 geneMRI studiesG alleleALT measurementsPUFA ratioPotential role
2010
Ethnic differences in lipoprotein subclasses in obese adolescents: importance of liver and intraabdominal fat accretion
D'Adamo E, Northrup V, Weiss R, Santoro N, Pierpont B, Savoye M, O'Malley G, Caprio S. Ethnic differences in lipoprotein subclasses in obese adolescents: importance of liver and intraabdominal fat accretion. American Journal Of Clinical Nutrition 2010, 92: 500-508. PMID: 20573788, PMCID: PMC2921534, DOI: 10.3945/ajcn.2010.29270.Peer-Reviewed Original ResearchConceptsHepatic fat fractionObese adolescentsLarge HDLEthnic differencesFat accretionCardiometabolic risk factorsDeleterious metabolic effectsNormal glucose toleranceLipoprotein particle numberVisceral fat depositionLiver fat contentLarge VLDL particlesLarge HDL particlesImportance of liverMagnetic resonance imagingAfrican AmericansSuccessive tertilesMultivariate adjustmentGlucose toleranceLiver fatLower triglyceridesLipoprotein concentrationsRisk factorsLipoprotein subclassesMetabolic effects
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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