2025
Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
Rubinelli L, Manzo O, Sungho J, Del Gaudio I, Bareja R, Marino A, Palikhe S, Di Mauro V, Bucci M, Falcone D, Elemento O, Ersoy B, Diano S, Sasset L, Di Lorenzo A. Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases. Nature Communications 2025, 16: 1968. PMID: 40000621, PMCID: PMC11862206, DOI: 10.1038/s41467-025-56869-9.Peer-Reviewed Original ResearchConceptsNogo-BEndothelial dysfunctionHFD miceCardiometabolic diseasesSphingolipid signalingDevelopment of therapeutic strategiesBioactive sphingolipidsCeramide degradationSphingosine-1-phosphateHepatic glucose productionIn vivo evidenceEndothelial cellsEndothelial specific deletionCeramideBiosynthesisHigh-fat dietPathological implicationsSphingolipidsGlucose productionHFDIn vivoMale miceMetabolic dysfunctionTherapeutic strategiesMetabolic disorders
2024
Ceramide synthesis inhibitors prevent lipid-induced insulin resistance through the DAG-PKCε-insulin receptorT1150 phosphorylation pathway
Xu W, Zhang D, Ma Y, Gaspar R, Kahn M, Nasiri A, Murray S, Samuel V, Shulman G. Ceramide synthesis inhibitors prevent lipid-induced insulin resistance through the DAG-PKCε-insulin receptorT1150 phosphorylation pathway. Cell Reports 2024, 43: 114746. PMID: 39302831, DOI: 10.1016/j.celrep.2024.114746.Peer-Reviewed Original ResearchLipid-induced hepatic insulin resistanceHepatic insulin resistancePhosphorylation pathwayAntisense oligonucleotidesCeramide synthesis inhibitorsLipid-induced insulin resistanceMyriocin treatmentCeramide synthesisDihydroceramide desaturaseInsulin resistanceHepatic ceramideMyriocinCeramideCeramide contentInsulin-sensitizing effectsPhosphorylationHepatic insulin sensitivityPathwaySynthetic pathwayDES1Glucose productionSynthesis inhibitorDGAT2DesaturaseInhibitionIL-10 constrains sphingolipid metabolism to limit inflammation
York A, Skadow M, Oh J, Qu R, Zhou Q, Hsieh W, Mowel W, Brewer J, Kaffe E, Williams K, Kluger Y, Smale S, Crawford J, Bensinger S, Flavell R. IL-10 constrains sphingolipid metabolism to limit inflammation. Nature 2024, 627: 628-635. PMID: 38383790, PMCID: PMC10954550, DOI: 10.1038/s41586-024-07098-5.Peer-Reviewed Original ResearchActivity of RelCeramide productionVery long chainFatty acid synthesis pathwayCeramide synthase 2Fatty acid homeostasisMetabolic fluxAvailable to cellsRegulatory nodesTranscription factorsCeramide accumulationSynthesis pathwayVLC ceramidesIL-10 deficiencyGene expressionSphingolipid metabolismAcid homeostasisAberrant activationIL-10Cell types1Innate immune cellsInflammatory gene expressionCeramideSignaling resultsGenetic deletion
2023
CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice
Hammerschmidt P, Steculorum S, Bandet C, Del Río-Martín A, Steuernagel L, Kohlhaas V, Feldmann M, Varela L, Majcher A, Quatorze Correia M, Klar R, Bauder C, Kaya E, Porniece M, Biglari N, Sieben A, Horvath T, Hornemann T, Brodesser S, Brüning J. CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice. Nature Communications 2023, 14: 7824. PMID: 38016943, PMCID: PMC10684560, DOI: 10.1038/s41467-023-42595-7.Peer-Reviewed Original ResearchConceptsMitochondrial stressSpecific ceramide speciesSteroidogenic factor 1Hypothalamic neuronsMitochondrial dynamicsMitochondrial morphologyCeramide synthaseObese miceGlucose homeostasisCeramide speciesCeramide synthesisConditional deletionHypothalamic lipotoxicityCultured hypothalamic neuronsAdverse metabolic effectsFactor 1High-fat dietImpairs glucose homeostasisDiet-induced alterationsCerS6DeletionHomeostasisGlucose toleranceCeramideInsulin sensitivityA defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels
Dutta D, Kanca O, Byeon S, Marcogliese P, Zuo Z, Shridharan R, Park J, Lin G, Ge M, Heimer G, Kohler J, Wheeler M, Kaipparettu B, Pandey A, Bellen H. A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels. Nature Metabolism 2023, 5: 1595-1614. PMID: 37653044, PMCID: PMC11151872, DOI: 10.1038/s42255-023-00873-0.Peer-Reviewed Original ResearchConceptsFatty acid synthesisFe-S cluster biogenesisMitochondrial fatty acid synthesisCeramide levelsMost eukaryotic cellsElevated ceramide levelsIron metabolismCluster biogenesisEukaryotic cellsLoss of functionCellular lipidomeEnoyl coenzymeNeurodegenerative phenotypeIron homeostasisHuman-derived fibroblastsMechanistic linkAcid synthesisCeramideMECRMetabolismNeurodegenerationMtFASBiogenesisLast stepMitochondria
2020
Decreased sphingolipid synthesis in children with 17q21 asthma–risk genotypes
Ono JG, Kim BI, Zhao Y, Christos PJ, Tesfaigzi Y, Worgall TS, Worgall S. Decreased sphingolipid synthesis in children with 17q21 asthma–risk genotypes. Journal Of Clinical Investigation 2020, 130: 921-926. PMID: 31929190, PMCID: PMC6994114, DOI: 10.1172/jci130860.Peer-Reviewed Original ResearchConceptsSphingolipid de novo synthesisNonallergic asthmaPeripheral blood cellsDe novo synthesisAirway hyperreactivityAllergic asthmaHuman asthmaAsthma pathogenesisChildhood asthmaAsthma riskAsthmaORMDL3 expressionAsthma susceptibilityBlood cellsNovo synthesisSphingolipid synthesisFuture therapeuticsDe novo sphingolipid synthesisChildrenORMDL3 overexpressionRiskDihydroceramideCeramideGenotypesHyperreactivity
2019
Lipidomics for wildlife disease etiology and biomarker discovery: a case study of pansteatitis outbreak in South Africa
Koelmel J, Ulmer C, Fogelson S, Jones C, Botha H, Bangma J, Guillette T, Luus-Powell W, Sara J, Smit W, Albert K, Miller H, Guillette M, Olsen B, Cochran J, Garrett T, Yost R, Bowden J. Lipidomics for wildlife disease etiology and biomarker discovery: a case study of pansteatitis outbreak in South Africa. Metabolomics 2019, 15: 38. PMID: 30838461, PMCID: PMC11005104, DOI: 10.1007/s11306-019-1490-9.Peer-Reviewed Original ResearchConceptsApplication of lipidomicsDiverse biological rolesWildlife studiesPossible disease mechanismsClasses of lipidsHigh-resolution tandem mass spectrometryLoskop DamBiological roleMozambique tilapiaCell deathMortality eventsPansteatitisLipidomicsOxidative damageDisease mechanismsAdipose tissuePromising biomarker candidatesBiomarker discoveryDisease etiologyTilapiaTandem mass spectrometryCeramideAquatic lifeLipidomeBiomarker candidates
2018
Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain
Lin G, Lee P, Chen K, Mao D, Tan K, Zuo Z, Lin W, Wang L, Bellen H. Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain. Cell Metabolism 2018, 28: 605-618.e6. PMID: 29909971, DOI: 10.1016/j.cmet.2018.05.019.Peer-Reviewed Original ResearchMeSH Keywordsalpha-SynucleinAnimalsBrainCell Line, TumorCeramidesDrosophilaDrosophila ProteinsFeedback, PhysiologicalFemaleGroup VI Phospholipases A2Group X Phospholipases A2HeLa CellsHumansLysosomesMaleMembrane FluidityMutationNeuronsNuclear ProteinsParkinson DiseaseRNA-Binding ProteinsSphingolipidsVesicular Transport ProteinsConceptsIPLA2-VIAImpairs synaptic transmissionEarly-onset parkinsonismSynaptic transmissionNeuroaxonal dystrophyParkinson's diseaseNeuronal functionBrain tissueNeurodegenerative disordersΑ-synucleinPLA2G6Ceramide levelsProgressive increaseNeurodegenerationLysosomal stressPositive feedback loopRetromer functionPhospholipid compositionCeramideGlycerol phospholipidsParkinsonismVPS35Desipramine
2015
Macrophage-specific de Novo Synthesis of Ceramide Is Dispensable for Inflammasome-driven Inflammation and Insulin Resistance in Obesity*
Camell CD, Nguyen KY, Jurczak MJ, Christian BE, Shulman GI, Shadel GS, Dixit VD. Macrophage-specific de Novo Synthesis of Ceramide Is Dispensable for Inflammasome-driven Inflammation and Insulin Resistance in Obesity*. Journal Of Biological Chemistry 2015, 290: 29402-29413. PMID: 26438821, PMCID: PMC4705943, DOI: 10.1074/jbc.m115.680199.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBone Marrow CellsCarrier ProteinsCeramidesDiet, High-FatDisease Models, AnimalFatty AcidsFemaleInflammasomesInflammationInsulin ResistanceLipidsMacrophagesMaleMiceMice, TransgenicMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinObesityOxidative StressSerine C-PalmitoyltransferaseConceptsDe novo synthesisNovo synthesisOverexpression of catalaseDietary lipid overloadSynthesis machineryTissue homeostasisCell-specific deletionInflammasome activationAdipose tissue homeostasisNLRP3 inflammasome activationMyeloid cell-specific deletionMetabolic pathwaysCeramide synthesisAlternate metabolic pathwaysCaspase-1 cleavageEnergy homeostasisLipid overloadCeramideLipid metabolismInflammasome-dependent mannerOxidative stressDanger signalsFat diet-induced obesityHomeostasisFatty acids
2009
Synthesis and biological activity of α-galactosyl ceramide KRN7000 and galactosyl (α1→2) galactosyl ceramide
Veerapen N, Brigl M, Garg S, Cerundolo V, Cox L, Brenner M, Besra G. Synthesis and biological activity of α-galactosyl ceramide KRN7000 and galactosyl (α1→2) galactosyl ceramide. Bioorganic & Medicinal Chemistry Letters 2009, 19: 4288-4291. PMID: 19502056, PMCID: PMC2722241, DOI: 10.1016/j.bmcl.2009.05.095.Peer-Reviewed Original Research
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