2020
O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity
Yang Y, Fu M, Li MD, Zhang K, Zhang B, Wang S, Liu Y, Ni W, Ong Q, Mi J, Yang X. O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity. Nature Communications 2020, 11: 181. PMID: 31924761, PMCID: PMC6954210, DOI: 10.1038/s41467-019-13914-8.Peer-Reviewed Original ResearchMeSH KeywordsAcetylglucosamineAnimalsCell Line, TumorDietFastingGene DeletionHEK293 CellsHeLa CellsHomeostasisHumansIntra-Abdominal FatLipolysisMaleMiceMice, Inbred C3HMice, Inbred C57BLMice, KnockoutN-AcetylglucosaminyltransferasesObesityPerilipin-1PhosphorylationProtein Processing, Post-TranslationalSignal TransductionConceptsDiet-induced obesityVisceral fatExcessive visceral fat accumulationPerilipin 1Visceral fat accumulationVisceral fat lossTreatment of obesityPrimary risk factorAdipose tissue homeostasisUnhealthy obesityRisk factorsEnhanced lipolysisInhibits lipolysisFat accumulationO-GlcNAcylationFat lossObesityFat lipolysisRelated diseasesLipolysisInducible deletionLipid dropletsHexosamine biosynthetic pathwayFatTissue homeostasis
2018
Adipocyte OGT governs diet-induced hyperphagia and obesity
Li MD, Vera NB, Yang Y, Zhang B, Ni W, Ziso-Qejvanaj E, Ding S, Zhang K, Yin R, Wang S, Zhou X, Fang EX, Xu T, Erion DM, Yang X. Adipocyte OGT governs diet-induced hyperphagia and obesity. Nature Communications 2018, 9: 5103. PMID: 30504766, PMCID: PMC6269424, DOI: 10.1038/s41467-018-07461-x.Peer-Reviewed Original ResearchConceptsSerine/threonine residuesN-acetylglucosamine transferaseNutrient cuesThreonine residuesTranscriptional activationO-GlcNAcylationLipid desaturationIntracellular proteinsOGTHigh-fat diet-induced hyperphagiaDevelopment of obesityBaseline food intakeSignaling contributesLipid signalsCB1 signalingBrain axisChronic dysregulationFood intakeMetabolic diseasesPalatable foodPharmacological manipulationHyperphagiaObesityFat sensorSignaling
2017
Calcium-dependent O-GlcNAc signaling drives liver autophagy in adaptation to starvation
Ruan HB, Ma Y, Torres S, Zhang B, Feriod C, Heck RM, Qian K, Fu M, Li X, Nathanson MH, Bennett AM, Nie Y, Ehrlich BE, Yang X. Calcium-dependent O-GlcNAc signaling drives liver autophagy in adaptation to starvation. Genes & Development 2017, 31: 1655-1665. PMID: 28903979, PMCID: PMC5647936, DOI: 10.1101/gad.305441.117.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, BiologicalAnimalsAutophagyAutophagy-Related Protein 5Autophagy-Related Protein-1 HomologCalcium SignalingCalcium-Calmodulin-Dependent Protein Kinase Type 2Cells, CulturedGlucagonHEK293 CellsHeLa CellsHumansInositol 1,4,5-Trisphosphate ReceptorsLiverMice, Inbred C57BLN-AcetylglucosaminyltransferasesNutritional Physiological PhenomenaConceptsAMPK-dependent phosphorylationLiver autophagyN-acetylglucosamine transferaseCalmodulin-dependent kinase IICalcium/calmodulin-dependent kinase IIWhole-body homeostasisULK proteinsNutrient homeostasisKinase IICalcium signalingAutophagic fluxGenetic ablationMetabolic adaptationAutophagyStarvationOGTPhosphorylationHomeostasisMouse liverProduction of glucoseKetone bodiesAdaptationSignalingProteinTransferase
2016
Metabolic Regulation of Gene Expression by Histone Lysine β-Hydroxybutyrylation
Xie Z, Zhang D, Chung D, Tang Z, Huang H, Dai L, Qi S, Li J, Colak G, Chen Y, Xia C, Peng C, Ruan H, Kirkey M, Wang D, Jensen LM, Kwon OK, Lee S, Pletcher SD, Tan M, Lombard DB, White KP, Zhao H, Li J, Roeder RG, Yang X, Zhao Y. Metabolic Regulation of Gene Expression by Histone Lysine β-Hydroxybutyrylation. Molecular Cell 2016, 62: 194-206. PMID: 27105115, PMCID: PMC5540445, DOI: 10.1016/j.molcel.2016.03.036.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesChromatin Assembly and DisassemblyDiabetic KetoacidosisDisease Models, AnimalEnergy MetabolismEpigenesis, GeneticFatty AcidsGene Expression RegulationGlucoseHEK293 CellsHistonesHumansHydroxybutyratesLiverLysineMice, Inbred C57BLPromoter Regions, GeneticProtein Processing, Post-TranslationalStarvationStreptozocinConceptsLysine β-hydroxybutyrylationΒ-hydroxybutyrylationActive gene promotersEpigenetic regulatory marksRNA-seq analysisHistone acetylation sitesChromatin regulationHistone marksChIP-seqAcetylation sitesProtein modificationGene promoterRegulatory marksDiverse functionsGene expressionMetabolic regulationMetabolic pathwaysCultured cellsPathophysiological statesRegulationExpressionNew avenuesKbhbMarksGenes
2014
O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat
Ruan HB, Dietrich MO, Liu ZW, Zimmer MR, Li MD, Singh JP, Zhang K, Yin R, Wu J, Horvath TL, Yang X. O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat. Cell 2014, 159: 306-317. PMID: 25303527, PMCID: PMC4509746, DOI: 10.1016/j.cell.2014.09.010.Peer-Reviewed Original ResearchConceptsAgRP neuronsFundamental cellular processesWhite fatN-acetylglucosamine (O-GlcNAc) modificationOrexigenic AgRP neuronsVoltage-dependent potassium channelsCellular processesGlcNAc transferaseDynamic physiological processesNuclear proteinsWhite adipose tissue browningPhysiological processesAdipose tissue browningDiet-induced obesityPhysiological relevanceTissue browningGenetic ablationBeige cellsEnergy metabolismInsulin resistanceNeuronal excitabilityPotassium channelsAdipose tissueCentral mechanismsNeurons
2012
O-GlcNAc Transferase/Host Cell Factor C1 Complex Regulates Gluconeogenesis by Modulating PGC-1α Stability
Ruan HB, Han X, Li MD, Singh JP, Qian K, Azarhoush S, Zhao L, Bennett AM, Samuel VT, Wu J, Yates JR, Yang X. O-GlcNAc Transferase/Host Cell Factor C1 Complex Regulates Gluconeogenesis by Modulating PGC-1α Stability. Cell Metabolism 2012, 16: 226-237. PMID: 22883232, PMCID: PMC3480732, DOI: 10.1016/j.cmet.2012.07.006.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBlotting, WesternChromatin ImmunoprecipitationChromatography, High Pressure LiquidGluconeogenesisHeat-Shock ProteinsHEK293 CellsHep G2 CellsHost Cell Factor C1HumansHyperglycemiaImmunoprecipitationLiverMiceMice, Inbred C57BLMultiprotein ComplexesN-AcetylglucosaminyltransferasesPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaProteomicsReal-Time Polymerase Chain ReactionTandem Mass SpectrometryTranscription FactorsConceptsHCF-1O-GlcNAcylationPGC-1αHost cell factor C1Hexosamine biosynthetic pathwayN-acetylglucosamine (O-GlcNAc) modificationDeubiquitinase BAP1Proteomic approachGlcNAc transferasePosttranslational modificationsNuclear proteinsBiosynthetic pathwayMaster regulatorKey regulatorFactor C1C1 complexOGTGlucose availabilityRegulatorProteinGluconeogenesisHepatic gluconeogenesisGlucose homeostasisComplexesHepatic knockdown
2008
Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance
Yang X, Ongusaha PP, Miles PD, Havstad JC, Zhang F, So WV, Kudlow JE, Michell RH, Olefsky JM, Field SJ, Evans RM. Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance. Nature 2008, 451: 964-969. PMID: 18288188, DOI: 10.1038/nature06668.Peer-Reviewed Original ResearchMeSH KeywordsAcetylglucosamineAnimalsCell MembraneChlorocebus aethiopsCOS CellsInsulinInsulin ResistanceLipid MetabolismLiverMaleMiceMice, Inbred C57BLN-AcetylglucosaminyltransferasesPhosphatidylinositol PhosphatesPhosphatidylinositolsPhosphorylationProtein Structure, TertiaryProtein TransportSecond Messenger SystemsConceptsO-GlcNAcSignal transductionPhosphoinositide-binding domainsPost-translational modificationsO-GlcNAc transferaseHexosamine biosynthetic pathwayInsulin signal transductionInsulin-responsive genesCellular regulationGlcNAc transferaseNutritional cuesNuclear proteinsBiosynthetic pathwayPlasma membraneProtein degradationNutrient sensorMolecular mechanismsN-acetylglucosamineTransductionPathwayTransferaseHepatic overexpressionGlucose fluxDynamic modificationMetabolic status
2006
Nuclear Receptor Expression Links the Circadian Clock to Metabolism
Yang X, Downes M, Yu RT, Bookout AL, He W, Straume M, Mangelsdorf DJ, Evans RM. Nuclear Receptor Expression Links the Circadian Clock to Metabolism. Cell 2006, 126: 801-810. PMID: 16923398, DOI: 10.1016/j.cell.2006.06.050.Peer-Reviewed Original ResearchConceptsNuclear receptor expressionReceptor expressionFat-soluble hormoneBrown adipose tissueKey metabolic tissuesPeripheral circadian clocksGlucose metabolismAdipose tissueDietary lipidsThyroid hormonesMetabolic tissuesKey target genesSkeletal muscleOrphan receptorNuclear receptorsEnergy metabolismNovel roleBasal metabolismHormoneMetabolismReceptorsCircadian clockExpression profilesMouse nuclear receptorsCircadian entrainment