2025
Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis
Sakuma I, Gaspar R, Nasiri A, Dufour S, Kahn M, Zheng J, LaMoia T, Guerra M, Taki Y, Kawashima Y, Yimlamai D, Perelis M, Vatner D, Petersen K, Huttasch M, Knebel B, Kahl S, Roden M, Samuel V, Tanaka T, Shulman G. Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2502978122. PMID: 40310463, PMCID: PMC12067271, DOI: 10.1073/pnas.2502978122.Peer-Reviewed Original ResearchConceptsCholine-deficient l-amino acid-defined high-fat dietBempedoic acidLiver fibrosisLiver diseaseL-amino acid-defined high-fat dietAdvanced liver diseaseCholesterol contentHSD17B13 variantsHigh-fat dietTotal liver cholesterol contentTreated miceActivate signaling pathwaysVariant rs738409Liver cholesterol contentLiver lipidsFibrotic responsePromote inflammationTherapeutic approachesSteatotic liver diseaseDietary cholesterol supplementationFibrosisHuman liver samplesI148MAntisense oligonucleotidesProgressive formTANGO2 is an acyl-CoA binding protein
Lujan A, Foresti O, Wojnacki J, Bigliani G, Brouwers N, Pena M, Androulaki S, Hashidate-Yoshida T, Kalyukina M, Novoselov S, Shindou H, Malhotra V. TANGO2 is an acyl-CoA binding protein. Journal Of Cell Biology 2025, 224: e202410001. PMID: 40015245, PMCID: PMC11867700, DOI: 10.1083/jcb.202410001.Peer-Reviewed Original ResearchConceptsAcyl-CoA binding proteinPeriphery of lipid dropletsAcyl-coenzyme A binding proteinA-binding proteinsAcyl-coenzyme AMitochondrial lumenHeme transportBinding proteinTANGO2Cellular localizationLipid dropletsStructural regionsLipid metabolismHeightened energy demandsMutationsProteinResiduesNrdEMetabolic crisisBindingMetabolismHemeSevere cardiomyopathyLipid
2024
A spatial expression atlas of the adult human proximal small intestine
Harnik Y, Yakubovsky O, Hoefflin R, Novoselsky R, Bahar Halpern K, Barkai T, Korem Kohanim Y, Egozi A, Golani O, Addadi Y, Kedmi M, Keidar Haran T, Levin Y, Savidor A, Keren-Shaul H, Mayer C, Pencovich N, Pery R, Shouval D, Tirosh I, Nachmany I, Itzkovitz S. A spatial expression atlas of the adult human proximal small intestine. Nature 2024, 632: 1101-1109. PMID: 39112711, DOI: 10.1038/s41586-024-07793-3.Peer-Reviewed Original ResearchConceptsExpression atlasSingle-molecule fluorescence in situ hybridizationLipid droplet assemblyAdult human gutFluorescence in situ hybridizationHuman proximal small intestineHuman small intestineHuman gutSpatial proteomicsProximal small intestineTip cellsGene expressionSmall intestineIron uptakeSpatial transcriptomicsVillus tip cellsImmune cell typesMouse small intestineCell typesDroplet assemblyImmunosuppressive rolePro-immunogenicAdult human small intestineT cellsZonated expressionSpartin-mediated lipid transfer facilitates lipid droplet turnover
Wan N, Hong Z, Parson M, Korfhage J, Burke J, Melia T, Reinisch K. Spartin-mediated lipid transfer facilitates lipid droplet turnover. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314093121. PMID: 38190532, PMCID: PMC10801920, DOI: 10.1073/pnas.2314093121.Peer-Reviewed Original Research
2023
LC3 conjugation to lipid droplets
Omrane M, Melia T, Thiam A. LC3 conjugation to lipid droplets. Autophagy 2023, 19: 3251-3253. PMID: 37599471, PMCID: PMC10621252, DOI: 10.1080/15548627.2023.2249390.Peer-Reviewed Original ResearchMeSH KeywordsAutophagosomesAutophagyAutophagy-Related Protein 8 FamilyAutophagy-Related ProteinsLipid DropletsConceptsLipid dropletsResponse to different signalsDegradation of lipid dropletsUbiquitin-conjugating enzymeLong-term-starved cellsLC3-interacting regionArtificial lipid dropletsPatatin-like phospholipase domainMicrotubule-associated protein 1 light chain 3 betaFYVE domainTethering factorsE2 enzymesLIR motifLD surfaceZinc fingerEndoplasmic reticulumLipidated LC3BPerilipin 1Phospholipase domainAutophagosome formationAssembly platformPromote degradationProlonged starvationSequestosome 1ZFYVE1/DFCP1LC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy
Omrane M, Ben M'Barek K, Santinho A, Nguyen N, Nag S, Melia T, Thiam A. LC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy. Developmental Cell 2023, 58: 1266-1281.e7. PMID: 37315562, PMCID: PMC10686041, DOI: 10.1016/j.devcel.2023.05.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagosomesAutophagyAutophagy-Related Protein 5HumansLipid DropletsMiceMicrotubule-Associated ProteinsConceptsProtein 1 light chain 3BLarge lipid dropletsLight chain 3BStarvation triggersLipidation reactionNoncanonical autophagyLysosomal pathwayAutophagic processStore lipidsAutophagy mechanismLipid dropletsATG3Large LDsProlonged starvationHuman liver cellsLC3BTimes of scarcityStarvationLiver cellsMacrolipophagyAutophagicClose proximityAutophagyATG5Microtubules
2022
Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation
Hong Z, Adlakha J, Wan N, Guinn E, Giska F, Gupta K, Melia TJ, Reinisch KM. Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation. Journal Of Cell Biology 2022, 221: e202207022. PMID: 36282247, PMCID: PMC9597353, DOI: 10.1083/jcb.202207022.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsFatty AcidsGlycerophospholipidsLipid DropletsLipid MetabolismMitochondriaMitochondrial ProteinsConceptsEndoplasmic reticulumLipid dropletsProtein-mediated transferLipid transport proteinsLipid droplet formationLD biologyMitochondrial proteinsSecretory pathwayMass spectrometry analysisTerminal domainMitochondrial morphologyTransport proteinsLipid transportersCellular membranesLD metabolismMembrane contactX-ray structureSpectrometry analysisOrganellesGlycerophospholipidsProteinHydrophobic cavityFatty acidsLipidsMembraneIdentification of lipid droplets in gut bacteria
Zhang K, Zhou C, Li Z, Li X, Zhou Z, Cheng L, Mirza A, Shi Y, Chen B, Zhang M, Cui L, Zhang C, Wei T, Zhang X, Zhang S, Liu P. Identification of lipid droplets in gut bacteria. Protein & Cell 2022, 14: 143-148. PMID: 36929002, PMCID: PMC10019568, DOI: 10.1093/procel/pwac015.Peer-Reviewed Original Researchd-Limonene inhibits the occurrence and progression of LUAD through suppressing lipid droplet accumulation induced by PM2.5 exposure in vivo and in vitro
Zhu T, Li Y, Feng T, Yang Y, Zhang K, Gao J, Quan X, Qian Y, Yu H, Qian B. d-Limonene inhibits the occurrence and progression of LUAD through suppressing lipid droplet accumulation induced by PM2.5 exposure in vivo and in vitro. Respiratory Research 2022, 23: 338. PMID: 36496421, PMCID: PMC9741803, DOI: 10.1186/s12931-022-02270-9.Peer-Reviewed Original ResearchConceptsLipid droplet accumulationHuman intervention trialsLung cancer patientsLung adenocarcinomaPM2.5 exposureProgression of LUADDroplet accumulationPulmonary fibrosisIntervention trialsCancer patientsMiR-195Trichrome stainingChinese Clinical Trial RegistrySerum miR-195Clinical Trials RegistryLipid metabolism disordersNormal lung epithelial cellsPotential preventive interventionsNormal lung tissuesDe novo lipogenesis pathwayMasson's trichrome stainingDevelopment of LUADOil red stainingLung epithelial cellsPotential intervention targets
2021
Eruptive xanthoma model reveals endothelial cells internalize and metabolize chylomicrons, leading to extravascular triglyceride accumulation
Cabodevilla AG, Tang S, Lee S, Mullick AE, Aleman JO, Hussain MM, Sessa WC, Abumrad NA, Goldberg IJ. Eruptive xanthoma model reveals endothelial cells internalize and metabolize chylomicrons, leading to extravascular triglyceride accumulation. Journal Of Clinical Investigation 2021, 131: e145800. PMID: 34128469, PMCID: PMC8203467, DOI: 10.1172/jci145800.Peer-Reviewed Original ResearchConceptsLPL-deficient miceScavenger receptor BISkin macrophagesEruptive xanthomasStudy of patientsLipid droplet biogenesisAccumulation of triglyceridesEndothelial cell barrierLipoprotein lipase hydrolysisChylomicron uptakeDroplet biogenesisReceptor BITG accumulationTissue uptakeTriglyceride accumulationDietary lipidsChylomicronsEndothelial cellsLipid accumulationAortic ECsLipid dropletsMacrophagesTriglyceridesHyperchylomicronemic patientsCultured ECs
2020
Screening of Drug-Induced Steatosis and Phospholipidosis Using Lipid Droplet-Selective Two-Photon Probes
Cho M, Seo M, Juvekar V, Jo J, Kim W, Choi K, Kim H. Screening of Drug-Induced Steatosis and Phospholipidosis Using Lipid Droplet-Selective Two-Photon Probes. Analytical Chemistry 2020, 92: 11223-11231. PMID: 32664717, DOI: 10.1021/acs.analchem.0c01728.Peer-Reviewed Original ResearchConceptsLipid dropletsStorage of neutral lipidsIncreased LDsSmall-molecule fluorescent probesResponse to oleic acidEndoplasmic reticulum stressAssociated with metabolic disordersDrug-induced steatosisEmission bandsTwo-photon probeFatty liver diseaseReticulum stressFixed cellsFluorescent probeLiver diseaseNarrow absorptionMetabolic disordersNeutral lipidsOrganellesTwo-photon microscopyInduce steatosisTwo-photon microscopy imagingScreening drugsMicroscopy imagesPhospholipidosisNovel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue
Li X, Yang L, Mao Z, Pan X, Zhao Y, Gu X, Eckel‐Mahan K, Zuo Z, Tong Q, Hartig S, Cheng X, Du G, Moore D, Bellen H, Sesaki H, Sun K. Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue. The FASEB Journal 2020, 34: 8265-8282. PMID: 32294302, PMCID: PMC7336545, DOI: 10.1096/fj.201903100rr.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumFlx/Function of Drp1Multicellular organismsPeroxisomal fissionDrp1 ablationER retentionLD dynamicsAutophagy functionER functionNovel roleDrp1LD morphologyKnockout modelsProtein 1Unilocular morphologyAdipose tissueLipid metabolismDynaminOrganellesCold exposureTissueOrganismsLarge sizeMultilocular structure
2019
Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III
Chang C, Weigel A, Ioannou M, Pasolli H, Xu C, Peale D, Shtengel G, Freeman M, Hess H, Blackstone C, Lippincott-Schwartz J. Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III. Journal Of Cell Biology 2019, 218: 2583-2599. PMID: 31227594, PMCID: PMC6683741, DOI: 10.1083/jcb.201902061.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAmino Acid MotifsATP Binding Cassette Transporter, Subfamily D, Member 1Biological TransportEndosomal Sorting Complexes Required for TransportFatty AcidsHeLa CellsHumansHydrolysisLauric AcidsLipid DropletsModels, BiologicalMutant ProteinsOncogene ProteinsPeroxisomesSpastinConceptsFA traffickingLipid dropletsESCRT-III componentsNeutral lipid storage organellesLipid storage organellesFatty acid traffickingAAA-ATPaseESCRT-IIIDual roleMIT domainFatty acidsStorage organellesContact sitesPathogenesis of diseaseFA metabolismTraffickingPeroxisomesSpastinIST1OrganellesCHMP1BInterrelated mechanismsLipid peroxidationContact formationATPaseNeuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity
Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, Pasolli HA, Xu CS, Pang S, Matthies D, Hess HF, Lippincott-Schwartz J, Liu Z. Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity. Cell 2019, 177: 1522-1535.e14. PMID: 31130380, DOI: 10.1016/j.cell.2019.04.001.Peer-Reviewed Original ResearchConceptsGene expression programsLipid dropletsFatty acidsToxic fatty acidsMitochondrial β-oxidationNeuron-astrocyte couplingExpression programsMetabolic coordinationFatty acid toxicityFA toxicityCoordinated mechanismFA metabolismΒ-oxidationLipid metabolismHyperactive neuronsAcid toxicityNeuronal activityDisease statesNeuronsMetabolismNeural activityLipid particlesAstrocytesBrainHomeostasisFABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation
Islam A, Kagawa Y, Miyazaki H, Shil SK, Umaru BA, Yasumoto Y, Yamamoto Y, Owada Y. FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation. Molecular Neurobiology 2019, 56: 5763-5779. PMID: 30680690, DOI: 10.1007/s12035-019-1489-2.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseROS toxicityLipid droplet formationLD accumulationPeroxiredoxin 1Stress-activated protein kinase/c-Jun N-terminal kinaseProtein kinase/c-Jun N-terminal kinaseP38 mitogen-activated protein kinaseC-Jun N-terminal kinaseReactive oxygen species stressRole of FABP7ROS inductionU87 human glioma cell lineN-terminal kinaseOxygen species stressActivation of apoptosisFABP7 overexpressionProtein bindsProtein kinaseLD formationLong-chain fatty acidsROS stressHuman glioma cell linesLipid dynamicsWild-type astrocytes
2018
The Inner Nuclear Membrane Takes On Lipid Metabolism
Merta H, Bahmanyar S. The Inner Nuclear Membrane Takes On Lipid Metabolism. Developmental Cell 2018, 47: 397-399. PMID: 30458132, DOI: 10.1016/j.devcel.2018.11.005.Peer-Reviewed Original ResearchMeSH KeywordsLipid DropletsLipid MetabolismLipidsMembrane ProteinsNuclear EnvelopeSaccharomyces cerevisiaeVPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites
Kumar N, Leonzino M, Hancock-Cerutti W, Horenkamp FA, Li P, Lees JA, Wheeler H, Reinisch KM, De Camilli P. VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites. Journal Of Cell Biology 2018, 217: 3625-3639. PMID: 30093493, PMCID: PMC6168267, DOI: 10.1083/jcb.201807019.Peer-Reviewed Original ResearchConceptsN-terminal portionAutophagy protein ATG2Membrane lipid homeostasisLate endosomes/lysosomesSecondary structure similarityLipid transport proteinsER contact sitesEndosomes/lysosomesHuman VPS13AVPS13 genesVps13Implicating defectsTransport proteinsLipid transportersContact sitesGenetic studiesLipid homeostasisLipid exchangeTransport roleProteinOrganellesVPS13ANeurodegenerative disordersStructure similarityHydrophobic cavity
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 inducesActivation
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
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