2012
5-Cholesten-3β,25-Diol 3-Sulfate Decreases Lipid Accumulation in Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model
Xu L, Kim JK, Bai Q, Zhang X, Kakiyama G, Min HK, Sanyal AJ, Pandak WM, Ren S. 5-Cholesten-3β,25-Diol 3-Sulfate Decreases Lipid Accumulation in Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model. Molecular Pharmacology 2012, 83: 648-658. PMID: 23258548, PMCID: PMC3583496, DOI: 10.1124/mol.112.081505.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl-CoA CarboxylaseAcetyltransferasesAnimalsCholesterol EstersDiet, High-FatFas ReceptorFatty AcidsFatty LiverFemaleGene ExpressionGlucose Tolerance TestGlycerol-3-Phosphate O-AcyltransferaseHydroxycholesterolsInflammationInsulinInsulin ResistanceInterleukin-1alphaInterleukin-1betaLipid MetabolismLipidsLiverMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseSignal TransductionSterol Regulatory Element Binding Protein 1Tumor Necrosis Factor-alphaConceptsNonalcoholic fatty liver diseaseHigh-fat dietLong-term treatmentAcute treatmentTolerance testLipid accumulationMouse modelDiet-induced NAFLD mouse modelNonalcoholic fatty liver disease (NAFLD) mouse modelSREBP-1cLipid homeostasisFatty liver diseaseLiver X receptor αNAFLD mouse modelGlucose tolerance testSerum lipid levelsInsulin tolerance testHepatic lipid accumulationDisease mouse modelDecreases lipid accumulationTumor necrosis factorLipid-induced inflammationAcetyl-CoA carboxylase 1X receptor αSREBP-1c expressionCholesterol metabolite, 5-cholesten-3β-25-diol-3-sulfate, promotes hepatic proliferation in mice
Zhang X, Bai Q, Kakiyama G, Xu L, Kim JK, Pandak WM, Ren S. Cholesterol metabolite, 5-cholesten-3β-25-diol-3-sulfate, promotes hepatic proliferation in mice. The Journal Of Steroid Biochemistry And Molecular Biology 2012, 132: 262-270. PMID: 22732306, PMCID: PMC3463675, DOI: 10.1016/j.jsbmb.2012.06.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell CycleCell ProliferationCholesterolCholesterol EstersDNA ReplicationGene Expression RegulationHydrocarbons, FluorinatedHydroxycholesterolsLiverLiver X ReceptorsMiceMice, Inbred C57BLOrphan Nuclear ReceptorsSignal TransductionSulfonamidesSulfotransferasesTissue DistributionUp-RegulationConceptsLiver X receptorHepatic proliferationSynthetic LXR agonist T0901317LXR agonist T0901317PCNA labeling indexDose-dependent mannerSuppresses cell proliferationOxysterol sulfationOxysterol sulfotransferaseProliferation gene expressionAgonist T0901317Cholesterol metabolitesLabeling indexEndogenous ligandLiver proliferationX receptorHepatic DNA replicationHepatocyte proliferationSREBP-1cNovel regulatory pathwayPCR arrayCell proliferationAdministrationPotent regulatorOxysterols25-Hydroxycholesterol-3-sulfate attenuates inflammatory response via PPARγ signaling in human THP-1 macrophages
Xu L, Shen S, Ma Y, Kim JK, Rodriguez-Agudo D, Heuman DM, Hylemon PB, Pandak WM, Ren S. 25-Hydroxycholesterol-3-sulfate attenuates inflammatory response via PPARγ signaling in human THP-1 macrophages. AJP Endocrinology And Metabolism 2012, 302: e788-e799. PMID: 22275753, PMCID: PMC3330710, DOI: 10.1152/ajpendo.00337.2011.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Inflammatory AgentsBlotting, WesternCell NucleusCholesterol EstersCytokinesCytosolEnzyme-Linked Immunosorbent AssayHumansHydroxycholesterolsHypoglycemic AgentsI-kappa B ProteinsLipopolysaccharidesMacrophagesNF-kappa BPPAR gammaProtein TransportReal-Time Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingRosiglitazoneSignal TransductionThiazolidinedionesConceptsNF-κB protein levelsPeroxisome proliferator-activated receptorInflammatory responseNuclear PPARγReporter gene assayLipid metabolismNuclear receptor peroxisome proliferator-activated receptorIL-1β expressionLiver X receptor ligandsProtein levelsActivation of PPARγHuman THP-1 macrophagesProliferator-activated receptorGene assayLuciferase activityTHP-1 macrophagesPPARγ-specific antagonistIκB/NF-κBX receptor ligandsIL-1βPromoter reporter gene assaysCholesterol metabolitesPPARγ activityPotent regulatory moleculesNF-κBOxysterol sulfation by cytosolic sulfotransferase suppresses liver X receptor/sterol regulatory element binding protein–1c signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcoholic fatty liver disease
Bai Q, Zhang X, Xu L, Kakiyama G, Heuman D, Sanyal A, Pandak WM, Yin L, Xie W, Ren S. Oxysterol sulfation by cytosolic sulfotransferase suppresses liver X receptor/sterol regulatory element binding protein–1c signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcoholic fatty liver disease. Metabolism 2012, 61: 836-845. PMID: 22225954, PMCID: PMC3342481, DOI: 10.1016/j.metabol.2011.11.014.Peer-Reviewed Original ResearchConceptsHepatic lipid levelsOxysterol sulfationSULT2B1b expressionLipid levelsLipid metabolismNonalcoholic fatty liver diseaseWestern blotFatty liver diseaseLiver X receptor αHigh-cholesterol dietReal-time reverse transcriptase-polymerase chain reactionHigh-fat dietReverse transcriptase-polymerase chain reactionTranscriptase-polymerase chain reactionAcetyl-CoA carboxylase 1X receptor αImportant endogenous regulatorLiver diseaseTotal cholesterolHepatic lipidsHepatic steatosisFatty acid synthasePolymerase chain reactionSterol regulatory element-binding proteinLung tissue
2010
Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells
Bai Q, Xu L, Kakiyama G, Runge-Morris MA, Hylemon PB, Yin L, Pandak WM, Ren S. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells. Atherosclerosis 2010, 214: 350-356. PMID: 21146170, PMCID: PMC3031658, DOI: 10.1016/j.atherosclerosis.2010.11.021.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCholesterol EstersChromatography, High Pressure LiquidEndothelial CellsFatty Acids, NonesterifiedGene Expression RegulationHumansHydrocarbons, FluorinatedHydroxycholesterolsLiver X ReceptorsOrphan Nuclear ReceptorsRNA, MessengerSignal TransductionSterol Regulatory Element Binding Protein 1SulfonamidesSulfotransferasesTime FactorsTransfectionTriglyceridesConceptsHuman aortic endothelial cellsLipid metabolismAortic endothelial cellsSULT2B1b overexpressionSREBP-1cEndothelial cellsIntracellular lipid homeostasisOxysterol sulfotransferaseReceptor agonistLipid levelsPresence of T0901317Cellular lipid levelsLipid homeostasisRecombinant adenovirusACC-1Protein levelsSULT2B1bSulfated metabolitesMetabolismCellular lipidsOverexpressionKey regulatorSimilar resultsCellsRegulation of Hepatocyte Lipid Metabolism and Inflammatory Response by 25‐Hydroxycholesterol and 25‐Hydroxycholesterol‐3‐sulfate
Xu L, Bai Q, Rodriguez‐Agudo D, Hylemon PB, Heuman DM, Pandak WM, Ren S. Regulation of Hepatocyte Lipid Metabolism and Inflammatory Response by 25‐Hydroxycholesterol and 25‐Hydroxycholesterol‐3‐sulfate. Lipids 2010, 45: 821-832. PMID: 20700770, DOI: 10.1007/s11745-010-3451-y.Peer-Reviewed Original ResearchConceptsSREBP-1 protein levelsAcetyl-CoA carboxylase 1Fatty acid synthaseLipid metabolismPromoter-reporter geneProtein levelsImportant regulatory moleculesNFkappaB-dependent genesHepatocyte lipid metabolismLXR/SREBPTarget genesFAS mRNA levelsReporter geneRegulatory moleculesKey enzymeNFkappaB nuclear translocationAcid synthasePrimary rat hepatocytesIkappaBalpha levelsCholesterol biosynthesisNuclear translocationGenesLuciferase activityPotent regulatorNFkappaB activation
2008
25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway
Ma Y, Xu L, Rodriguez-Agudo D, Li X, Heuman DM, Hylemon PB, Pandak WM, Ren S. 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. AJP Endocrinology And Metabolism 2008, 295: e1369-e1379. PMID: 18854425, PMCID: PMC2603552, DOI: 10.1152/ajpendo.90555.2008.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell ProliferationCells, CulturedCholesterol EstersDNA-Binding ProteinsDose-Response Relationship, DrugGene Expression RegulationHumansHydroxycholesterolsLipid MetabolismLipidsLiver X ReceptorsMacrophagesModels, BiologicalOrphan Nuclear ReceptorsReceptors, Cytoplasmic and NuclearSignal TransductionSterol Regulatory Element Binding Protein 1SulfatesConceptsLXR/SREBPFatty acid synthaseSREBP-1Lipid metabolismFatty acid synthetic pathwayKey transcriptional regulatorMacrophage lipid metabolismImportant regulatory moleculesTHP-1-derived macrophagesMature proteinTranscriptional regulatorsAcetyl-CoA carboxylase 1MRNA levelsFAS mRNA levelsKey proteinsGene expressionRegulatory moleculesHuman THP-1-derived macrophagesAcid synthaseSREBPLipid synthesisOxysterol sulfationLXR ligandsCarboxylase 1Cell proliferation