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
Diagnostic Accuracy of Transient Elastography in Hepatosteatosis in Youth With Obesity
Tas E, Sundararajan D, Lo J, Morelli N, Garcia-Reyes Y, Ware M, Rahat H, Ou X, Na X, Sundaram S, Severn C, Pyle L, Børsheim E, Vajravelu M, Muzumdar R, Dranoff J, Cree M. Diagnostic Accuracy of Transient Elastography in Hepatosteatosis in Youth With Obesity. Journal Of The Endocrine Society 2024, 8: bvae110. PMID: 38895640, PMCID: PMC11185182, DOI: 10.1210/jendso/bvae110.Peer-Reviewed Original ResearchMRI fat fractionMagnetic resonance imagingPolycystic ovary syndromeVibration-controlled transient elastographyTransient elastographyDiagnostic accuracyDiagnostic accuracy of transient elastographyAccuracy of transient elastographyReceiver-operating characteristic curveFat fractionHepatosteatosis groupSignificant obesityDiagnostic performanceClinical trialsYouden indexLiver diseaseChildhood obesityHigh riskSteatotic liver diseaseLiver fatObesityResonance imagingCharacteristic curveHepatosteatosisDiagnostic methods
2023
Effects of short‐term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial
Tas E, Landes R, Diaz E, Bai S, Ou X, Buchmann R, Na X, Muzumdar R, Børsheim E, Dranoff J. Effects of short‐term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial. Obesity 2023, 31: 2740-2749. PMID: 37731271, PMCID: PMC11519784, DOI: 10.1002/oby.23887.Peer-Reviewed Original ResearchConceptsHigh-intensity interval trainingCardiorespiratory fitnessOral glucose tolerance testDual-energy X-ray absorptiometryAttenuation parameter (CAP) scoreIntrahepatic triglyceride contentSerum alanine aminotransferaseGlucose tolerance testSteatotic liver diseaseX-ray absorptiometryLiver magnetic resonanceCardiometabolic markersCardiometabolic healthExercise trainingHIIT protocolsLiver diseaseLiver fatExercise protocolTolerance testCRF testAlanine aminotransferaseInterval trainingMRI-PDFFTriglyceride contentObesityPerformance of an automated deep learning algorithm to identify hepatic steatosis within noncontrast computed tomography scans among people with and without HIV
Torgersen J, Akers S, Huo Y, Terry J, Carr J, Ruutiainen A, Skanderson M, Levin W, Lim J, Taddei T, So‐Armah K, Bhattacharya D, Rentsch C, Shen L, Carr R, Shinohara R, McClain M, Freiberg M, Justice A, Re V. Performance of an automated deep learning algorithm to identify hepatic steatosis within noncontrast computed tomography scans among people with and without HIV. Pharmacoepidemiology And Drug Safety 2023, 32: 1121-1130. PMID: 37276449, PMCID: PMC10527049, DOI: 10.1002/pds.5648.Peer-Reviewed Original ResearchConceptsSevere hepatic steatosisHepatic steatosisHIV statusLiver attenuationHounsfield unitsPredictive valueRadiologist assessmentUS Veterans Health AdministrationNoncontrast abdominal CTVeterans Health AdministrationCross-sectional studySample of patientsNegative predictive valueReal-world studyPositive predictive valueAbdominal CTLiver fatTomography scanSteatosisCT imagesHealth AdministrationPharmacoepidemiologic studiesRadiologist reviewHIVPercent agreementGenomic analysis of lean individuals with NAFLD identifies monogenic disorders in a prospective cohort study
Zheng M, Huang D, Konkwo C, Agrawal S, Khera A, Loomba R, Vilarinho S, Ajmera V. Genomic analysis of lean individuals with NAFLD identifies monogenic disorders in a prospective cohort study. JHEP Reports 2023, 5: 100692. PMID: 36937991, PMCID: PMC10017416, DOI: 10.1016/j.jhepr.2023.100692.Peer-Reviewed Original ResearchNon-alcoholic fatty liver diseaseLean non-alcoholic fatty liver diseaseFatty liver diseaseBiopsy-proven non-alcoholic fatty liver diseaseLiver diseaseWhole-exome sequencingLean patientsVisceral adiposityPatient 2Liver fatLean individualsMonogenic disordersMagnetic Resonance Imaging AssessmentExome sequencingHigh liver fatProspective cohort studyCohort of patientsEvaluation of patientsHereditary fructose intoleranceHomozygous pathogenic mutationNAFLD subtypesUnique genetic mutationsCohort studyLiver biopsyRare heterozygous mutations
2022
Lower Hepatic Fat Is Associated With Improved Insulin Secretion in a High-Risk Prediabetes Subphenotype During Lifestyle Intervention
Wagner R, Heni M, Kantartzis K, Sandforth A, Machann J, Schick F, Peter A, Fritsche L, Szendrödi J, Pfeiffer A, Schürmann A, Blüher M, Hauner H, Seissler J, Bornstein S, Roden M, Stefan N, Birkenfeld A, White M, Häring H, Fritsche A. Lower Hepatic Fat Is Associated With Improved Insulin Secretion in a High-Risk Prediabetes Subphenotype During Lifestyle Intervention. Diabetes 2022, 72: 362-366. PMID: 36525512, PMCID: PMC9935494, DOI: 10.2337/db22-0441.Peer-Reviewed Original ResearchConceptsInsulin secretionLifestyle interventionLiver fatOral glucose tolerance testHigh liver fatLifestyle intervention studyGlucose tolerance testHigh-risk clustersHepatic fatTolerance testInsulin sensitivitySpecific subphenotypesIntervention studiesSecretionTime pointsInterventionPrediabetesGlycemic traitsFatSubphenotypesGlycemiaCluster 3
2020
Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health
Abulizi A, Cardone RL, Stark R, Lewandowski SL, Zhao X, Hillion J, Ma L, Sehgal R, Alves TC, Thomas C, Kung C, Wang B, Siebel S, Andrews ZB, Mason GF, Rinehart J, Merrins MJ, Kibbey RG. Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health. Cell Metabolism 2020, 32: 751-766.e11. PMID: 33147485, PMCID: PMC7679013, DOI: 10.1016/j.cmet.2020.10.006.Peer-Reviewed Original ResearchConceptsInsulin secretionInsulin sensitivityPK activatorWhole-body metabolic healthPK activationMetabolic homeostasisPeripheral insulin sensitivityHFD-fed ratsEndogenous glucose productionPreclinical rodent modelsHigher insulin contentPreclinical rationaleLiver fatMetabolic healthMarkers of differentiationIslet functionRodent modelsGlucose homeostasisInsulin contentPancreatic isletsGlucose productionGlucose turnoverMitochondrial PEPCKSecretionHomeostasisFibroblast Growth Factor-21 to Adiponectin Ratio: A Potential Biomarker to Monitor Liver Fat in Children With Obesity
Tas E, Bai S, Ou X, Mercer K, Lin H, Mansfield K, Buchmann R, Diaz EC, Oden J, Børsheim E, Adams SH, Dranoff J. Fibroblast Growth Factor-21 to Adiponectin Ratio: A Potential Biomarker to Monitor Liver Fat in Children With Obesity. Frontiers In Endocrinology 2020, 11: 654. PMID: 33071964, PMCID: PMC7533567, DOI: 10.3389/fendo.2020.00654.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseMagnetic resonance imagingIntrahepatic triglyceridesPercent changePotential biomarkersClinical weight loss programSerum fibroblast growth factorFibroblast growth factor 21Liver fat percentFatty liver diseaseWeight loss programGrowth factor 21Non-invasive biomarkersFibroblast growth factorCourse diseaseSerum FGF21Adiponectin ratioFinal visitAdiponectin levelsLiver biopsyLiver diseaseObese childrenLoss programLiver fatFactor 21
2018
The interplay of canonical and noncanonical Wnt signaling in metabolic syndrome
Abou Ziki M, Mani A. The interplay of canonical and noncanonical Wnt signaling in metabolic syndrome. Nutrition Research 2018, 70: 18-25. PMID: 30049588, PMCID: PMC6320319, DOI: 10.1016/j.nutres.2018.06.009.Peer-Reviewed Original ResearchConceptsMetabolic syndromeLow density lipoprotein clearanceVascular smooth muscle proliferationEnd-organ complicationsCanonical WntSmooth muscle proliferationLow-density lipoproteinDe novo lipogenesisInsulin receptor expressionTranscription factor 7Growth factor βRas homolog gene family member AExtracellular matrix depositionCardiometabolic abnormalitiesLiver inflammationFamily member AInsulin resistanceLipoprotein clearanceLiver fatHepatic fibrosisSevere manifestationsLDL receptor-related protein 6Receptor expressionCardiovascular diseaseMuscle proliferationImproved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease
Ma J, Hennein R, Liu C, Long MT, Hoffmann U, Jacques PF, Lichtenstein AH, Hu FB, Levy D. Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease. Gastroenterology 2018, 155: 107-117. PMID: 29604292, PMCID: PMC6035111, DOI: 10.1053/j.gastro.2018.03.038.Peer-Reviewed Original ResearchConceptsMediterranean-style diet scoreNonalcoholic fatty liver diseaseAlternative Healthy Eating IndexGenetic risk scoreHigh genetic risk scoreDiet quality changesIncident fatty liverFatty liver diseaseLiver fat accumulationFatty liverDiet scoreLiver fatRisk scoreFramingham Heart StudyAHEI scoreLiver diseaseFat accumulationHeart StudyHarvard Food Frequency QuestionnaireDiet qualityFood frequency questionnaireThird Generation cohortsHealthy Eating IndexAssociation of changesStandard deviation increase
2017
Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans
Horst K, Gilijamse PW, Versteeg RI, Ackermans MT, Nederveen AJ, la Fleur SE, Romijn JA, Nieuwdorp M, Zhang D, Samuel VT, Vatner DF, Petersen KF, Shulman GI, Serlie MJ. Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans. Cell Reports 2017, 19: 1997-2004. PMID: 28591572, PMCID: PMC5469939, DOI: 10.1016/j.celrep.2017.05.035.Peer-Reviewed Original ResearchConceptsHepatic insulin resistanceInsulin resistanceHepatic steatosisObese subjectsPKCε activationTissue-specific insulin sensitivityHepatic ceramide contentPeripheral insulin resistanceHepatic lipid accumulationPathogenesis of NAFLDLiver biopsyIntrahepatic triglyceridesLiver fatInsulin sensitivityAdipose tissueTranslational evidenceSteatosisLipid accumulationCeramide contentPKCε translocationSubjectsMolecular mechanismsDiacylglycerol contentHumansActivation
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
High Visceral and Low Abdominal Subcutaneous Fat Stores in the Obese Adolescent A Determinant of an Adverse Metabolic Phenotype
Taksali SE, Caprio S, Dziura J, Dufour S, Calí A, Goodman TR, Papademetris X, Burgert TS, Pierpont BM, Savoye M, Shaw M, Seyal AA, Weiss R. High Visceral and Low Abdominal Subcutaneous Fat Stores in the Obese Adolescent A Determinant of an Adverse Metabolic Phenotype. Diabetes 2007, 57: 367-371. PMID: 17977954, DOI: 10.2337/db07-0932.Peer-Reviewed Original ResearchConceptsMetabolic syndromeObese adolescentsInsulin resistanceVisceral fatSubcutaneous fatAdverse metabolic phenotypeC-reactive proteinSevere metabolic complicationsAbdominal subcutaneous fatBMI z-scoreProton magnetic resonance spectroscopyMulti-ethnic cohortFat-free massSubcutaneous fat depotsMagnetic resonance imagingSubcutaneous fat storesMetabolic complicationsTotal adiponectinHepatic fatLiver fatTriglyceride levelsInterleukin-6Visceral depotsOdds ratioC-peptide
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