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 tissueBile acid synthesis impedes tumor-specific T cell responses during liver cancer
Varanasi S, Chen D, Liu Y, Johnson M, Miller C, Ganguly S, Lande K, LaPorta M, Hoffmann F, Mann T, Teneche M, Casillas E, Mangalhara K, Mathew V, Sun M, Jensen I, Farsakoglu Y, Chen T, Parisi B, Deota S, Havas A, Lee J, Chung H, Schietinger A, Panda S, Williams A, Farber D, Dhar D, Adams P, Feng G, Shadel G, Sundrud M, Kaech S. Bile acid synthesis impedes tumor-specific T cell responses during liver cancer. Science 2025, 387: 192-201. PMID: 39787217, PMCID: PMC12166762, DOI: 10.1126/science.adl4100.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAnimalsBile Acids and SaltsCarcinoma, HepatocellularCD8-Positive T-LymphocytesCell Line, TumorEndoplasmic Reticulum StressHepatocytesHumansImmune Checkpoint InhibitorsImmunotherapyLithocholic AcidLiver NeoplasmsMiceOxidative StressProgrammed Cell Death 1 ReceptorTumor MicroenvironmentUrsodeoxycholic AcidConceptsTumor-specific T-cell responsesT cell responsesAnti-programmed cell death protein 1Ursodeoxycholic acidCell death protein 1CD8<sup>+</sup> T cellsBile acidsFeatures of human hepatocellular carcinomaImprove tumor immunotherapyInfluence antitumor immunityT cell functionReduced tumor growthBA synthesisLiver cancer modelCancer model systemsHuman hepatocellular carcinomaLandscape of cancerAntitumor immunityTumor immunotherapySecondary bile acidsOrgan-specific metabolitesEndoplasmic reticulum stressT cellsCancer modelsDietary intake
2023
Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition
Sakuma I, Gaspar R, Luukkonen P, Kahn M, Zhang D, Zhang X, Murray S, Golla J, Vatner D, Samuel V, Petersen K, Shulman G. Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2312666120. PMID: 38127985, PMCID: PMC10756285, DOI: 10.1073/pnas.2312666120.Peer-Reviewed Original Research
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 individualsVariants
2019
Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis
Genet G, Boyé K, Mathivet T, Ola R, Zhang F, Dubrac A, Li J, Genet N, Henrique Geraldo L, Benedetti L, Künzel S, Pibouin-Fragner L, Thomas JL, Eichmann A. Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis. Nature Communications 2019, 10: 2350. PMID: 31138815, PMCID: PMC6538628, DOI: 10.1038/s41467-019-10359-x.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAnimalsCell MovementCell PolarityCell ProliferationCell SurvivalEndocytosisEndothelial CellsIntercellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMiceMice, KnockoutNeovascularization, PhysiologicNerve Tissue Proteinsp21-Activated KinasesReceptors, ImmunologicRetinal VesselsVascular Endothelial Growth Factor Receptor-2ConceptsEndophilin A2Endothelial cell migrationSprouting angiogenesisCell migrationFront-rear polarityBAR domain proteinsFront-rear polarizationClathrin-independent internalizationSpecific endocytic pathwaysVEGFR2 endocytosisEndocytic pathwayAngiogenesis defectsEffector PAKTip cellsSlit-RoboActivation of VEGFR2Downstream activationVEGFR2 internalizationCell behaviorPathological angiogenesisCritical mediatorEndocytosisPathological conditions
2018
The 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, PMCID: PMC12136689, 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 metabolismEndoplasmic reticulum acyltransferase with prokaryotic substrate preference contributes to triacylglycerol assembly in Chlamydomonas
Kim Y, Terng EL, Riekhof WR, Cahoon EB, Cerutti H. Endoplasmic reticulum acyltransferase with prokaryotic substrate preference contributes to triacylglycerol assembly in Chlamydomonas. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 1652-1657. PMID: 29382746, PMCID: PMC5816170, DOI: 10.1073/pnas.1715922115.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAlgal ProteinsChlamydomonas reinhardtiiChloroplastsEndoplasmic ReticulumPhylogenySubstrate SpecificityTriglyceridesConceptsUnicellular green algaEndoplasmic reticulum membraneLysophosphatidic acid acyltransferaseChloroplastic pathwayPrecursor biosynthesisTAG precursorsNitrogen deprivationTriacylglycerol assemblyAssembly pathwayGreen algaTAG accumulationAcid acyltransferaseAcyl donor substratesReticulum membraneBiomaterial productionDonor substrateChlamydomonasTriacylglycerol metabolismPalmitoyl-CoAAcyltransferasePathwayMajor roleBiosynthesisAlgaRNA
2017
Crystal structure of E. coli apolipoprotein N-acyl transferase
Lu G, Xu Y, Zhang K, Xiong Y, Li H, Cui L, Wang X, Lou J, Zhai Y, Sun F, Zhang XC. Crystal structure of E. coli apolipoprotein N-acyl transferase. Nature Communications 2017, 8: 15948. PMID: 28885614, PMCID: PMC5500890, DOI: 10.1038/ncomms15948.Peer-Reviewed Original ResearchConceptsApolipoprotein N-acyl transferaseN-acyl transferaseTM domainN-terminal cysteine residueThree-step pathwayGram-negative bacteriaLid loopTransmembrane domainPeriplasmic sideTM helicesCysteine residuesLipid modificationLipid donorCatalytic cavityAcceptor substrateLipid bilayersLipid leafletCatalytic centerAcyl chainsCrystal structurePathwayTransferaseLateral openingDomainProtein
2016
Identification of a Chlamydomonas plastidial 2‐lysophosphatidic acid acyltransferase and its use to engineer microalgae with increased oil content
Yamaoka Y, Achard D, Jang S, Legéret B, Kamisuki S, Ko D, Schulz‐Raffelt M, Kim Y, Song W, Nishida I, Li‐Beisson Y, Lee Y. Identification of a Chlamydomonas plastidial 2‐lysophosphatidic acid acyltransferase and its use to engineer microalgae with increased oil content. Plant Biotechnology Journal 2016, 14: 2158-2167. PMID: 27133096, PMCID: PMC5096022, DOI: 10.1111/pbi.12572.Peer-Reviewed Original ResearchConceptsAcid acyltransferaseNitrogen-deficient conditionsOil contentPlastid membranesBiosynthetic pathwayStorage lipidsBiosynthetic processesReinhardtii cellsMicroalgal oil productionMolecular toolsSn-2 positionEnzyme assaysAlgal lipidsPhosphatidic acidCommon precursorMicroalgaeAcyltransferaseCoAMembranePlastidsLPAATChlamydomonasReinhardtiiLipidsGenes
2015
The Protein Acyl Transferase ZDHHC21 Modulates α1 Adrenergic Receptor Function and Regulates Hemodynamics
Marin EP, Jozsef L, Di Lorenzo A, Held KF, Luciano AK, Melendez J, Milstone LM, Velazquez H, Sessa WC. The Protein Acyl Transferase ZDHHC21 Modulates α1 Adrenergic Receptor Function and Regulates Hemodynamics. Arteriosclerosis Thrombosis And Vascular Biology 2015, 36: 370-379. PMID: 26715683, PMCID: PMC4984414, DOI: 10.1161/atvbaha.115.306942.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAdrenergic alpha-1 Receptor AgonistsAnimalsAortaBlood PressureDose-Response Relationship, DrugEpinephrineFibroblastsGenotypeHeart RateHEK293 CellsHemodynamicsHumansHypotensionLipoylationMesenteric ArteriesMice, Inbred C57BLMice, Mutant StrainsMutationNorepinephrinePhenotypePhenylephrineReceptors, Adrenergic, alpha-1Signal TransductionTachycardiaTime FactorsTransfectionVasoconstrictionConceptsProtein acyl transferasesNovel molecular modeZDHHC familyLipid palmitateZDHHC enzymesVascular toneNumerous proteinsPossible molecular mechanismsProtein localizationAdrenergic receptor gene expressionGene expressionMolecular mechanismsVascular functionBiochemical studiesReceptor gene expressionAcyl transferaseMolecular modePalmitoylationΑ1-adrenergic receptor agonistTelemetry studiesInfusion of phenylephrinePhysiological studiesΑ1-adrenergic receptorsReceptor functionAdrenergic receptor agonist
2014
The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis
Huang LS, Mathew B, Li H, Zhao Y, Ma SF, Noth I, Reddy SP, Harijith A, Usatyuk PV, Berdyshev EV, Kaminski N, Zhou T, Zhang W, Zhang Y, Rehman J, Kotha SR, Gurney TO, Parinandi NL, Lussier YA, Garcia JG, Natarajan V. The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2014, 189: 1402-1415. PMID: 24779708, PMCID: PMC4098083, DOI: 10.1164/rccm.201310-1917oc.Peer-Reviewed Original ResearchMeSH Keywords1-Acylglycerol-3-Phosphate O-AcyltransferaseAcyltransferasesAnimalsBiomarkersCardiolipinsCohort StudiesDisease Models, AnimalHumansIdiopathic Pulmonary FibrosisIn Situ HybridizationLeukocytes, MononuclearMiceMitochondriaPredictive Value of TestsPulmonary FibrosisRNA, MessengerSensitivity and SpecificitySeverity of Illness IndexConceptsPeripheral blood mononuclear cellsIdiopathic pulmonary fibrosisPulmonary fibrosisMurine modelAlveolar epithelial cellsOverall survivalReactive oxygen species generationLysocardiolipin acyltransferaseOxygen species generationCarbon monoxide diffusion capacityRadiation-induced pulmonary fibrosisPulmonary function outcomesEpithelial cellsBlood mononuclear cellsPreclinical murine modelsNovel therapeutic approachesSpecies generationBleomycin challengeLung inflammationLung protectionPulmonary functionFunction outcomesLung fibrosisMononuclear cellsFibrotic lungs
2012
Endothelial Cell Palmitoylproteomic Identifies Novel Lipid-Modified Targets and Potential Substrates for Protein Acyl Transferases
Marin EP, Derakhshan B, Lam TT, Davalos A, Sessa WC. Endothelial Cell Palmitoylproteomic Identifies Novel Lipid-Modified Targets and Potential Substrates for Protein Acyl Transferases. Circulation Research 2012, 110: 1336-1344. PMID: 22496122, PMCID: PMC3428238, DOI: 10.1161/circresaha.112.269514.Peer-Reviewed Original ResearchMeSH KeywordsAcetyltransferasesAcyltransferasesAmino Acid SequenceAnimalsChlorocebus aethiopsCOS CellsEndothelial CellsHEK293 CellsHuman Umbilical Vein Endothelial CellsHumansLipoylationMolecular Sequence DataPlatelet Endothelial Cell Adhesion Molecule-1ProteomicsRNA, Small InterferingSubstrate SpecificitySuperoxide DismutaseSuperoxide Dismutase-1ConceptsProtein acyl transferasesAcyl-biotinyl exchangeProtein S-palmitoylationPlatelet endothelial cell adhesion molecule-1Posttranslational lipid modificationRole of palmitoylationEndothelial cell adhesion molecule-1Acyl transferaseEndothelial cell biologyPalmitoyl proteinsS-palmitoylationPosttranslational attachmentProtein localizationCysteine side chainsCell biologyNuclear localizationPalmitoylationLipid modificationEC biologyThioester bondCell adhesion molecule-1Superoxide dismutase 1Functional roleCell surfacePotential substrates
2010
Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system
Wu M, Huang B, Graham M, Raimondi A, Heuser JE, Zhuang X, De Camilli P. Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system. Nature Cell Biology 2010, 12: 902-908. PMID: 20729836, PMCID: PMC3338250, DOI: 10.1038/ncb2094.Peer-Reviewed Original ResearchActinsAcyltransferasesAdenosine TriphosphateAnimalsAntibodiesBridged Bicyclo Compounds, HeterocyclicCarrier ProteinsCattleCell LineCell MembraneCell Membrane StructuresCell-Free SystemClathrinCoated Pits, Cell-MembraneCytosolDynaminsEndocytosisFatty Acid-Binding ProteinsFibroblastsGuanosine 5'-O-(3-Thiotriphosphate)Guanosine TriphosphateHumansImaging, Three-DimensionalMiceMicroscopy, Electron, TransmissionMicroscopy, FluorescenceModels, BiologicalPotoroidaeRatsReceptors, TransferrinThiazolidines
2009
PapA3 Is an Acyltransferase Required for Polyacyltrehalose Biosynthesis in Mycobacterium tuberculosis *
Hatzios SK, Schelle MW, Holsclaw CM, Behrens CR, Botyanszki Z, Lin FL, Carlson BL, Kumar P, Leary JA, Bertozzi CR. PapA3 Is an Acyltransferase Required for Polyacyltrehalose Biosynthesis in Mycobacterium tuberculosis *. Journal Of Biological Chemistry 2009, 284: 12745-12751. PMID: 19276083, PMCID: PMC2676004, DOI: 10.1074/jbc.m809088200.Peer-Reviewed Original ResearchConceptsUnusual cell wallBiosynthetic gene clusterSulfolipid-1Cell wall moleculesTrehalose-based glycolipidsGene clusterBiosynthetic machineryPutative acyltransferaseBacterial lipid extractsCell wallMutant strainBiosynthesisWall moleculesPalmitoyl groupsGenesGlycolipidsM. tuberculosisPathogenic M. tuberculosisAcyltransferaseAcyltransferase activityPAT productionTrehaloseLipid extractsComplementationMycobacterium tuberculosis
2008
Starter unit specificity directs genome mining of polyketide synthase pathways in fungi
Crawford JM, Vagstad AL, Ehrlich KC, Townsend CA. Starter unit specificity directs genome mining of polyketide synthase pathways in fungi. Bioorganic Chemistry 2008, 36: 16-22. PMID: 18215412, PMCID: PMC3200548, DOI: 10.1016/j.bioorg.2007.11.002.Peer-Reviewed Original ResearchConceptsHybrid metabolitesPathogenic fungus Coccidioides immitisPolyketide synthase pathwayHuman fungal pathogenSAT domainAflatoxin clusterGenome miningSynthase subunitsPolyketide synthasePKS clustersACP domainStarter unitProtein databasePolyketide synthesisFungal pathogensFunctional similarityHexanoyl-CoA.Fatty acid productsEscherichia coliSynthase pathwayFungiFungus Coccidioides immitisAspergillus speciesPathwayDomain
2006
Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages
Perera RM, Zoncu R, Lucast L, De Camilli P, Toomre D. Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 19332-19337. PMID: 17158794, PMCID: PMC1693868, DOI: 10.1073/pnas.0609795104.Peer-Reviewed Original ResearchConceptsTotal internal reflection fluorescence microscopySynaptojanin 1CCP formationMulticolor total internal reflection fluorescence microscopyClathrin-coated pit dynamicsClathrin-coated pitsClathrin-dependent endocytosisEndocytic clathrin adaptorsSynaptic vesicle recyclingReflection fluorescence microscopyCell-free systemClathrin adaptorsPolyphosphoinositide phosphataseGenetic manipulationVesicle recyclingPit dynamicsIntact cellsSplice variantsFunctional studiesFluorescence microscopyEndophilinTemporal recruitmentDirect interactionIsoformsPredominant isoformIdentification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase
Fernández-Hernando C, Fukata M, Bernatchez PN, Fukata Y, Lin MI, Bredt DS, Sessa WC. Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase. Journal Of Cell Biology 2006, 174: 369-377. PMID: 16864653, PMCID: PMC2064233, DOI: 10.1083/jcb.200601051.Peer-Reviewed Original ResearchConceptsHuman endothelial cellsComplementary DNAPalmitoylation-deficient mutantHuman embryonic kidney 293 cellsEmbryonic kidney 293 cellsEndothelial nitric oxide synthaseEndothelial cellsKidney 293 cellsDHHC enzymesN-myristoylationS-palmitoylationNew GolgiSubcellular localizationCDNA clonesPlasma membraneLipid modificationCytoplasmic aspectENOS localizationGolgi apparatusRegulatory roleENOS palmitoylationPalmitoyl transferaseGolgiNitric oxide synthaseAcyl transferasePalmitoylation of the EGFR Ligand Spitz by Rasp Increases Spitz Activity by Restricting Its Diffusion
Miura GI, Buglino J, Alvarado D, Lemmon MA, Resh MD, Treisman JE. Palmitoylation of the EGFR Ligand Spitz by Rasp Increases Spitz Activity by Restricting Its Diffusion. Developmental Cell 2006, 10: 167-176. PMID: 16459296, DOI: 10.1016/j.devcel.2005.11.017.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAnimalsBase SequenceBiological Transport, ActiveCell LineCell MembraneCysteineDNADrosophilaDrosophila ProteinsEpidermal Growth FactorErbB ReceptorsFemaleGenes, InsectIn Vitro TechniquesLigandsMaleMembrane ProteinsModels, BiologicalMutagenesis, Site-DirectedMutationOvaryPalmitic AcidRecombinant ProteinsTransfectionWings, AnimalConceptsEpidermal growth factor receptorDrosophila epidermal growth factor receptorEGFR ligand SpitzPlasma membrane associationN-terminal cysteine residueLigand SpitzMembrane associationWnt familyDevelopmental functionsGrowth factor receptorCysteine residuesBiological functionsLipid modificationPalmitoylationIntracellular proteinsCultured cellsCell membraneFactor receptorSpitzReduced activityVivoTransmembraneHedgehogProteinActivity
2005
Retinoid processing proteins in the ocular ciliary epithelium.
Salvador-Silva M, Ghosh S, Bertazolli-Filho R, Boatright JH, Nickerson JM, Garwin GG, Saari JC, Coca-Prados M. Retinoid processing proteins in the ocular ciliary epithelium. Molecular Vision 2005, 11: 356-65. PMID: 15928609.Peer-Reviewed Original ResearchAcyltransferasesAlcohol OxidoreductasesAnimalsATP-Binding Cassette TransportersBlotting, WesternCarrier ProteinsCattleCells, CulturedChromatography, High Pressure LiquidCiliary Bodycis-trans-IsomerasesEye ProteinsFluorescent Antibody Technique, IndirectGene Expression RegulationHumansImmunohistochemistryPigment Epithelium of EyeProtein TransportRabbitsRetinoidsRetinol-Binding ProteinsRetinol-Binding Proteins, CellularReverse Transcriptase Polymerase Chain ReactionRNA, Messenger
2002
Mutations in the midway Gene Disrupt a Drosophila Acyl Coenzyme A: Diacylglycerol Acyltransferase
Buszczak M, Lu X, Segraves WA, Chang TY, Cooley L. Mutations in the midway Gene Disrupt a Drosophila Acyl Coenzyme A: Diacylglycerol Acyltransferase. Genetics 2002, 160: 1511-1518. PMID: 11973306, PMCID: PMC1462074, DOI: 10.1093/genetics/160.4.1511.Peer-Reviewed Original ResearchConceptsEgg chambersDiacylglycerol acyltransferaseNurse cellsAcyl coenzyme AMutant egg chambersNurse cell deathCell deathInsect cells resultsEgg chamber developmentCoenzyme AGermline apoptosisDrosophila oogenesisCytoplasm transportDGAT activityCells resultsChamber developmentNeutral lipidsGenesLipid metabolismDiacylglycerolApoptosisAcyltransferaseDrosophilaCellsOogenesis
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