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
Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis
Ghouse J, Sveinbjörnsson G, Vujkovic M, Seidelin A, Gellert-Kristensen H, Ahlberg G, Tragante V, Rand S, Brancale J, Vilarinho S, Lundegaard P, Sørensen E, Erikstrup C, Bruun M, Jensen B, Brunak S, Banasik K, Ullum H, Verweij N, Lotta L, Baras A, Mirshahi T, Carey D, Kaplan D, Lynch J, Morgan T, Schwantes-An T, Dochtermann D, Pyarajan S, Tsao P, Laisk T, Mägi R, Kozlitina J, Tybjærg-Hansen A, Jones D, Knowlton K, Nadauld L, Ferkingstad E, Björnsson E, Ulfarsson M, Sturluson Á, Sulem P, Pedersen O, Ostrowski S, Gudbjartsson D, Stefansson K, Olesen M, Chang K, Holm H, Bundgaard H, Stender S. Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis. Nature Genetics 2024, 56: 827-837. PMID: 38632349, PMCID: PMC11096111, DOI: 10.1038/s41588-024-01720-y.Peer-Reviewed Original ResearchMeSH KeywordsAlanine TransaminaseCarcinoma, HepatocellularCase-Control StudiesCohort StudiesFemalegamma-GlutamyltransferaseGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansLipaseLiver CirrhosisLiver NeoplasmsMaleMembrane ProteinsMultifactorial InheritancePolymorphism, Single NucleotideRisk FactorsConceptsMulti-ancestry genome-wide association studyPolygenic risk scoresRare variant analysisVariant analysisGenome-wide association studiesRare coding variantsHepatocellular carcinomaLow alanine aminotransferaseRisk associationAlcohol intakePrioritized genesGenetic architectureNear genesAlanine aminotransferaseRisk scoreHepatic lipid metabolismAssociation studiesLiver cirrhosisGenetic underpinningsPNPLA3 p.Cirrhosis to hepatocellular carcinomaRisk of cirrhosisLiver function testsLipid metabolismGenes
2023
Crawling toward obsolescence: The extended lifespan of amylase for pancreatitis
Kanaparthy N, Loza A, Hauser R. Crawling toward obsolescence: The extended lifespan of amylase for pancreatitis. PLOS ONE 2023, 18: e0296180. PMID: 38127992, PMCID: PMC10734915, DOI: 10.1371/journal.pone.0296180.Peer-Reviewed Original ResearchSerial serum lipase testing after the initial diagnostic workup for inpatients with acute pancreatitis: What is the evidence?
Magier S, Muniraj T, Merchant N. Serial serum lipase testing after the initial diagnostic workup for inpatients with acute pancreatitis: What is the evidence? Cleveland Clinic Journal Of Medicine 2023, 90: 341-343. PMID: 37263664, DOI: 10.3949/ccjm.90a.22060.Peer-Reviewed Original Research
2022
Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes
Yu X, Tong L, Zhang L, Yang Y, Xiao X, Zhu Y, Wang P, Cheng G. Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes. PLOS Pathogens 2022, 18: e1010552. PMID: 35679229, PMCID: PMC9182268, DOI: 10.1371/journal.ppat.1010552.Peer-Reviewed Original ResearchConceptsJapanese encephalitis virusYellow fever virusZika virusDengue virusSindbis virusGlobal public healthBroad-spectrum virucidal activityEffective prophylacticLipase activityViral envelope structureViral infectionSevere human diseasesEncephalitis virusAedes aegypti midgutVirucidal activityEtiological agentTremendous burdenFever virusVirusMost arbovirusesPublic healthVector-borne diseasesAegypti midgutDiseaseVirucidal abilityA multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation
Vujkovic M, Ramdas S, Lorenz KM, Guo X, Darlay R, Cordell HJ, He J, Gindin Y, Chung C, Myers RP, Schneider CV, Park J, Lee KM, Serper M, Carr RM, Kaplan DE, Haas ME, MacLean MT, Witschey WR, Zhu X, Tcheandjieu C, Kember RL, Kranzler HR, Verma A, Giri A, Klarin DM, Sun YV, Huang J, Huffman JE, Creasy KT, Hand NJ, Liu CT, Long MT, Yao J, Budoff M, Tan J, Li X, Lin HJ, Chen YI, Taylor KD, Chang RK, Krauss RM, Vilarinho S, Brancale J, Nielsen JB, Locke AE, Jones MB, Verweij N, Baras A, Reddy KR, Neuschwander-Tetri BA, Schwimmer JB, Sanyal AJ, Chalasani N, Ryan KA, Mitchell BD, Gill D, Wells AD, Manduchi E, Saiman Y, Mahmud N, Miller DR, Reaven PD, Phillips LS, Muralidhar S, DuVall SL, Lee JS, Assimes TL, Pyarajan S, Cho K, Edwards TL, Damrauer SM, Wilson PW, Gaziano JM, O’Donnell C, Khera AV, Grant SFA, Brown CD, Tsao PS, Saleheen D, Lotta LA, Bastarache L, Anstee QM, Daly AK, Meigs JB, Rotter JI, Lynch JA, Rader D, Voight B, Chang K. A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation. Nature Genetics 2022, 54: 761-771. PMID: 35654975, PMCID: PMC10024253, DOI: 10.1038/s41588-022-01078-z.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSingle nucleotide polymorphismsAssociation studiesMillion Veteran ProgramGenome-wide significanceGenetic architectureAdditional lociPleiotropy analysisInflammatory traitsLociNew insightsVeteran ProgramChronic ALT elevationTraitsExternal replicationRadiological validationReplication
2021
Role of candidate gene variants in modulating the risk and severity of alcoholic hepatitis
Beaudoin JJ, Liang T, Tang Q, Banini BA, Shah VH, Sanyal AJ, Chalasani NP, Gawrieh S. Role of candidate gene variants in modulating the risk and severity of alcoholic hepatitis. Alcohol Clinical And Experimental Research 2021, 45: 709-719. PMID: 33616244, PMCID: PMC8076096, DOI: 10.1111/acer.14581.Peer-Reviewed Original ResearchConceptsPatatin-like phospholipase domain-containing protein 3Effects of variantsCopy number variantsAcyltransferase domainDomain-containing protein 3Genetic basisCandidate genesCandidate gene variantsGenetic variantsNumber variantsHaptoglobin geneIndividual variantsProtein 3Member 2AllelesGenesGene variantsRisk allelesTransmembrane 6Affected individualsVariantsIdentification of a Metabolic, Transcriptomic, and Molecular Signature of Patatin‐Like Phospholipase Domain Containing 3–Mediated Acceleration of Steatohepatitis
Banini BA, Kumar DP, Cazanave S, Seneshaw M, Mirshahi F, Santhekadur PK, Wang L, Guan HP, Oseini AM, Alonso C, Bedossa P, Koduru SV, Min H, Sanyal AJ. Identification of a Metabolic, Transcriptomic, and Molecular Signature of Patatin‐Like Phospholipase Domain Containing 3–Mediated Acceleration of Steatohepatitis. Hepatology 2021, 73: 1290-1306. PMID: 33131062, PMCID: PMC8046714, DOI: 10.1002/hep.31609.Peer-Reviewed Original Research
2020
Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program
Serper M, Vujkovic M, Kaplan DE, Carr RM, Lee KM, Shao Q, Miller DR, Reaven PD, Phillips LS, O’Donnell C, Meigs JB, Wilson PWF, Vickers-Smith R, Kranzler HR, Justice AC, Gaziano JM, Muralidhar S, Pyarajan S, DuVall SL, Assimes TL, Lee JS, Tsao PS, Rader DJ, Damrauer SM, Lynch JA, Saleheen D, Voight BF, Chang KM, . Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program. PLOS ONE 2020, 15: e0237430. PMID: 32841307, PMCID: PMC7447043, DOI: 10.1371/journal.pone.0237430.Peer-Reviewed Original ResearchMeSH Keywords17-Hydroxysteroid DehydrogenasesAbdomenAdaptor Proteins, Signal TransducingAgedAlanine TransaminaseElectronic Health RecordsFemaleGenetic LociGenetic Predisposition to DiseaseGenetic VariationHumansLipaseLiverLysophospholipaseMaleMembrane ProteinsMiddle AgedNon-alcoholic Fatty Liver DiseasePhenotypeRisk FactorsVeteransConceptsMetabolic risk factorsNAFLD phenotypeAlanine aminotransferaseUnits/LElectronic health recordsAdvanced fibrosisRisk factorsMillion Veteran ProgramAlcohol consumptionNon-invasive criteriaNormal alanine aminotransferaseNAFLD fibrosis scorePopulation-based studyGenetic variantsFatty liver phenotypeVeteran ProgramPNPLA3 locusNAFLD riskLiver biopsyLiver diseaseFibrosis scoreEHR reviewUS veteransBiopsy dataAbdominal imagingGlucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis
Perry RJ, Zhang D, Guerra MT, Brill AL, Goedeke L, Nasiri AR, Rabin-Court A, Wang Y, Peng L, Dufour S, Zhang Y, Zhang XM, Butrico GM, Toussaint K, Nozaki Y, Cline GW, Petersen KF, Nathanson MH, Ehrlich BE, Shulman GI. Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis. Nature 2020, 579: 279-283. PMID: 32132708, PMCID: PMC7101062, DOI: 10.1038/s41586-020-2074-6.Peer-Reviewed Original ResearchConceptsHepatic steatosisType 2Nonalcoholic fatty liver diseaseDiet-induced hepatic steatosisFatty liver diseasePlasma glucagon concentrationsHepatic adipose triglyceride lipaseHepatic acetyl-CoA contentHepatic glucose productionRatio of insulinHepatic glucose metabolismInositol triphosphate receptorAdipose triglyceride lipaseMitochondrial oxidationMitochondrial fat oxidationGlucose intoleranceLiver diseaseGlucagon concentrationsInsulin resistancePortal veinAcetyl-CoA contentHepatic lipolysisGlucagon biologyGlucose metabolismKnockout mice
2019
The association study of lipid metabolism gene polymorphisms with AMD identifies a protective role for APOE‐E2 allele in the wet form in a Northern Spanish population
Fernández‐Vega B, García M, Olivares L, Álvarez L, González‐Fernández A, Artime E, Cueto A, Cobo T, Coca‐Prados M, Vega J, González‐Iglesias H. The association study of lipid metabolism gene polymorphisms with AMD identifies a protective role for APOE‐E2 allele in the wet form in a Northern Spanish population. Acta Ophthalmologica 2019, 98: e282-e291. PMID: 31654486, DOI: 10.1111/aos.14280.Peer-Reviewed Original ResearchConceptsAge-related macular degenerationWet age-related macular degenerationNorthern Spanish patientsLipid metabolism genesSpanish patientsSingle nucleotide polymorphismsProtective roleAMD casesNorthern Spanish populationApoE E2 alleleDry AMD casesCase-control studyAPOE ε2 alleleSpanish populationMetabolism gene polymorphismsABCA1 rs1883025Peripheral bloodHealthy controlsMacular degenerationAdditional association studiesGene polymorphismsLPL rs12678919APOE genePatientsCarrier genotypeComparison of biochemical parameters among DPP4 inhibitor users and other oral hypoglycaemic drug users: a cross-sectional study from Anuradhapura, Sri Lanka
Rathish D, Jayasumana C, Agampodi S. Comparison of biochemical parameters among DPP4 inhibitor users and other oral hypoglycaemic drug users: a cross-sectional study from Anuradhapura, Sri Lanka. Journal Of Health, Population And Nutrition 2019, 38: 3. PMID: 30674350, PMCID: PMC6343272, DOI: 10.1186/s41043-019-0160-x.Peer-Reviewed Original ResearchConceptsDPP4 inhibitor usersCross-sectional studyDrug usersInhibitor usersDipeptidyl peptidase-4 inhibitor treatmentType 2 diabetes mellitusComparative cross-sectional studyBiochemical parametersIncretin-based therapiesMann-Whitney U testSignificant differencesHigh lipase levelsPrevious Asian studiesDPP4i groupDPP4i usersOral hypoglycaemicsALT levelsDiabetes mellitusLipase levelsDPP4 inhibitorsSerum lipaseInhibitor treatmentU testPancreatic amylaseHbA1c
2017
Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing
Camell CD, Sander J, Spadaro O, Lee A, Nguyen KY, Wing A, Goldberg EL, Youm YH, Brown CW, Elsworth J, Rodeheffer MS, Schultze JL, Dixit VD. Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature 2017, 550: 119-123. PMID: 28953873, PMCID: PMC5718149, DOI: 10.1038/nature24022.Peer-Reviewed Original ResearchAdipocytesAdipose TissueAgingAnimalsCaspase 1CatecholaminesGene Expression ProfilingGene Expression RegulationGrowth Differentiation Factor 3InflammasomesLipaseLipolysisMacrophagesMiceMonoamine OxidaseMonoamine Oxidase InhibitorsNLR Family, Pyrin Domain-Containing 3 ProteinNorepinephrineSterol EsterasePhenotypic spectrum of autosomal recessive congenital ichthyosis due to PNPLA1 mutation
Boyden LM, Craiglow BG, Hu RH, Zhou J, Browning J, Eichenfield L, Lim YL, Luu M, Randolph LM, Ginarte M, Fachal L, Rodriguez‐Pazos L, Vega A, Kramer D, Yosipovitch G, Vahidnezhad H, Youssefian L, Uitto J, Lifton RP, Paller AS, Milstone LM, Choate KA. Phenotypic spectrum of autosomal recessive congenital ichthyosis due to PNPLA1 mutation. British Journal Of Dermatology 2017, 177: 319-322. PMID: 28403545, PMCID: PMC5522355, DOI: 10.1111/bjd.15570.Peer-Reviewed Original Research
2015
Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver
Martinez-Lopez N, Garcia-Macia M, Sahu S, Athonvarangkul D, Liebling E, Merlo P, Cecconi F, Schwartz GJ, Singh R. Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver. Cell Metabolism 2015, 23: 113-127. PMID: 26698918, PMCID: PMC4715637, DOI: 10.1016/j.cmet.2015.10.008.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytes, BrownAdipose Tissue, BrownAmino Acid SequenceAnimalsAutophagyCold TemperatureFemaleHypothalamusLipaseLipid DropletsLipolysisLiverLysosomesMaleMice, Inbred C57BLMice, TransgenicMicrotubule-Associated ProteinsMolecular Sequence DataNeuronsOxygen ConsumptionPro-OpiomelanocortinConceptsBrown adipose tissuePOMC neuronsLipid utilizationPeripheral tissuesAdipose tissueProopiomelanocortin neuronsInter-organ communicationCentral autophagyCold-induced activationATGLAutophagosome marker LC3LipolysisNeuronsTargeted activationLipase ATGLLipophagyIntegrative physiologyTissueMiceLiverAutophagyAutophagy proteinsCytosolic lipasesCold inducesActivationPANCREATITIS OR NOT? – Elevated lipase and amylase in ICU patients
Muniraj T, Dang S, Pitchumoni CS. PANCREATITIS OR NOT? – Elevated lipase and amylase in ICU patients. Journal Of Critical Care 2015, 30: 1370-1375. PMID: 26411523, DOI: 10.1016/j.jcrc.2015.08.020.Peer-Reviewed Original ResearchConceptsAcute pancreatitisAssociated co-morbid conditionsIntensive care unit patientsCare unit patientsCo-morbid conditionsNon-pancreatic diseaseElevated lipaseClinical pancreatitisMost patientsUnit patientsICU patientsIll patientsSerum levelsICU settingPancreatitisPatientsPancreatic enzymesClinical diagnosisTypical symptomsDifferent causesDiseaseElevationHyperamylasemiaHyperlipasemiaAmylase
2014
Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting
Wilfling F, Thiam AR, Olarte MJ, Wang J, Beck R, Gould TJ, Allgeyer ES, Pincet F, Bewersdorf J, Farese RV, Walther TC. Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting. ELife 2014, 3: e01607. PMID: 24497546, PMCID: PMC3913038, DOI: 10.7554/elife.01607.Peer-Reviewed Original ResearchMeSH KeywordsADP-Ribosylation Factor 1AnimalsBiological TransportCell LineCoat Protein Complex ICOP-Coated VesiclesDrosophila melanogasterDrosophila ProteinsEndoplasmic ReticulumHumansLipaseLipid DropletsLipolysisMiceNanoparticlesParticle SizePhospholipidsRNA InterferenceSurface TensionTime FactorsTransfectionTriglyceridesConceptsCellular lipid dropletsLipid dropletsProtein machineryProtein targetingUbiquitous organellesVesicle traffickingLD surfaceSpecific proteinsKey enzymeLD morphologyMembrane precursorsMachineryMetabolic energyProteinNeutral lipidsTG storageEnzymeUnclear mechanismsAmount of phospholipidsRecent evidenceOrganellesCOPITraffickingTriacylglycerolsBuds
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 roleRisk Factors Associated With Biliary Pancreatitis in Children
H. M, Bai HX, Park AJ, Latif SU, Mistry PK, Pashankar D, Northrup VS, Bhandari V, Husain SZ. Risk Factors Associated With Biliary Pancreatitis in Children. Journal Of Pediatric Gastroenterology And Nutrition 2012, 54: 651-656. PMID: 22002481, PMCID: PMC3626418, DOI: 10.1097/mpg.0b013e31823a897d.Peer-Reviewed Original ResearchConceptsBiliary pancreatitisRisk factorsIndependent predictorsAspartate aminotransferaseTertiary care hospitalManagement of childrenMultiple logistic regressionMedian serum amylaseCare hospitalProspective studyAcute pancreatitisSerum amylaseHispanic ethnicityPancreatitisTimes higher probabilityGallstonesGallstone casesLogistic regressionOlder childrenHispanic childrenObesityChildrenOptimal evaluationAminotransferaseBlack children
2011
Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents
Santoro N, Zhang CK, Zhao H, Pakstis AJ, Kim G, Kursawe R, Dykas DJ, Bale AE, Giannini C, Pierpont B, Shaw MM, Groop L, Caprio S. Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents. Hepatology 2011, 55: 781-789. PMID: 22105854, PMCID: PMC3288435, DOI: 10.1002/hep.24806.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdolescentApolipoprotein C-IIIBlack or African AmericanChildFatty LiverFemaleGene FrequencyGenetic Predisposition to DiseaseHaplotypesHispanic or LatinoHumansLipaseLipoproteins, VLDLMaleMembrane ProteinsObesityPolymorphism, Single NucleotideRisk FactorsTriglyceridesWhite PeopleConceptsFatty liverObese childrenSingle nucleotide polymorphismsTriglyceride levelsOral glucose tolerance testGlucokinase regulatory proteinGlucose tolerance testHepatic fat accumulationAccumulation of triglyceridesLow-density lipoproteinElevated triglyceridesLarge VLDLTolerance testFat accumulationObese youthGlucokinase regulatory protein geneMagnetic resonancePNPLA3LiverRs1260326African AmericansTriglyceridesLipoproteinChildrenNucleotide polymorphisms
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