2021
Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis
Zhang X, McDonald JG, Aryal B, Canfrán-Duque A, Goldberg EL, Araldi E, Ding W, Fan Y, Thompson BM, Singh AK, Li Q, Tellides G, Ordovás-Montanes J, García Milian R, Dixit VD, Ikonen E, Suárez Y, Fernández-Hernando C. Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2107682118. PMID: 34782454, PMCID: PMC8617522, DOI: 10.1073/pnas.2107682118.Peer-Reviewed Original ResearchConceptsCholesterol biosynthetic intermediatesBiosynthetic intermediatesDependent inflammasome activationSingle-cell transcriptomicsMitochondrial reactive oxygen species productionFoam cell formationMacrophage foam cellsReactive oxygen species productionHuman coronary artery lesionsConversion of desmosterolTranscriptomic analysisMacrophage cholesterol metabolismPhysiological contextOxygen species productionLiver X receptor ligandsApoptosis-associated speck-like proteinRetinoid X receptor activationX receptor ligandsInflammasome activationAtherosclerotic plaquesSpeck-like proteinCholesterol homeostasisMacrophage inflammasome activationKey moleculesCell formationMicroRNA regulation of cholesterol metabolism
Citrin KM, Fernández‐Hernando C, Suárez Y. MicroRNA regulation of cholesterol metabolism. Annals Of The New York Academy Of Sciences 2021, 1495: 55-77. PMID: 33521946, PMCID: PMC8938903, DOI: 10.1111/nyas.14566.Peer-Reviewed Original ResearchConceptsDifferent cell typesCell typesMultiple mRNA targetsCholesterol homeostasisSmall noncoding RNAsMicroRNA activityCholesterol-laden cellsMicroRNA regulationCholesterol metabolismMRNA targetsNoncoding RNAsPosttranscriptional levelGene expressionSpecialized functionsMicroRNAsCurrent knowledgeTarget interactionsHomeostasisMetabolismPathwayExpressionMultiple stagesRNARegulationDistinctive effects
2020
ANGPTL4: a multifunctional protein involved in metabolism and vascular homeostasis.
Fernández-Hernando C, Suárez Y. ANGPTL4: a multifunctional protein involved in metabolism and vascular homeostasis. Current Opinion In Hematology 2020, 27: 206-213. PMID: 32205586, PMCID: PMC9013473, DOI: 10.1097/moh.0000000000000580.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-Like Protein 4AnimalsCapillary PermeabilityCarcinogenesisHumansLipid MetabolismNeovascularization, PathologicStem CellsConceptsStem cell regulationPotential therapeutic targetLipid metabolismCell-specific functionsSpecific molecular eventsNonmetabolic functionsRegulatory circuitsMultifunctional proteinTherapeutic targetUnanticipated roleInvolvement of ANGPTL4Molecular eventsCell regulationPhysiological roleTherapeutic applicationsPredominant expressionVascular biologyPotential therapeutic applicationsVascular homeostasisPathophysiological conditionsDifferent disease settingsANGPTL4MetabolismFirst discoveryBiological effects
2019
ANGPTL4 in Metabolic and Cardiovascular Disease
Aryal B, Price NL, Suarez Y, Fernández-Hernando C. ANGPTL4 in Metabolic and Cardiovascular Disease. Trends In Molecular Medicine 2019, 25: 723-734. PMID: 31235370, PMCID: PMC6779329, DOI: 10.1016/j.molmed.2019.05.010.Peer-Reviewed Original ResearchConceptsCardiovascular diseaseLipoprotein lipaseRisk of atherosclerosisRole of ANGPTL4Type 2 diabetesLow-density lipoproteinFatty acidsMurine studiesPeripheral tissuesRich lipoproteinsLPL activityANGPTL4 functionsDensity lipoproteinMetabolic diseasesPossible autocrineParacrine formsDiseaseANGPTL4Disease developmentLipoproteinRecent findingsRiskTissueDifferent tissuesAtherosclerosis
2018
Brown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis
Singh AK, Aryal B, Chaube B, Rotllan N, Varela L, Horvath TL, Suárez Y, Fernández-Hernando C. Brown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis. Molecular Metabolism 2018, 11: 59-69. PMID: 29627378, PMCID: PMC6001401, DOI: 10.1016/j.molmet.2018.03.011.Peer-Reviewed Original ResearchConceptsBrown adipose tissueAdipose tissueAbsence of ANGPTL4Lipoprotein metabolismLPL activityShort-term HFD feedingTriglyceride-rich lipoprotein catabolismLipoprotein lipaseRole of ANGPTL4Novel mouse modelAcute cold exposureGlucose toleranceHFD feedingFatty acidsLipoprotein catabolismWhole body lipidGlucose homeostasisMouse modelGlucose metabolismTAG clearanceBAT resultsLipid metabolismANGPTL4Cold exposureFA oxidationAbsence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis
Aryal B, Singh AK, Zhang X, Varela L, Rotllan N, Goedeke L, Chaube B, Camporez JP, Vatner DF, Horvath TL, Shulman GI, Suárez Y, Fernández-Hernando C. Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis. JCI Insight 2018, 3: e97918. PMID: 29563332, PMCID: PMC5926923, DOI: 10.1172/jci.insight.97918.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAllelesAngiopoietin-Like Protein 4AnimalsAtherosclerosisBody WeightChemokinesCytokinesDiet, High-FatDiet, WesternFatty AcidsGene Expression ProfilingGene Expression RegulationGene Knockout TechniquesGlucoseInsulinIntegrasesIntercellular Signaling Peptides and ProteinsLipid MetabolismLipoprotein LipaseLipoproteinsLiverMaleMiceMice, Inbred C57BLMice, KnockoutMusclesObesityProprotein Convertase 9TriglyceridesConceptsAngiopoietin-like protein 4High-fat dietEctopic lipid depositionLipid depositionGlucose toleranceLipoprotein lipaseShort-term high-fat dietSevere metabolic abnormalitiesProgression of atherosclerosisMajor risk factorTriacylglycerol-rich lipoproteinsFatty acid uptakeAdipose tissue resultsProatherogenic lipoproteinsCardiometabolic diseasesMetabolic abnormalitiesKO miceRisk factorsWhole body lipidMetabolic disordersGlucose metabolismLPL activityAdipose tissueGenetic ablationRapid clearanceGenetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance
Price NL, Singh AK, Rotllan N, Goedeke L, Wing A, Canfrán-Duque A, Diaz-Ruiz A, Araldi E, Baldán Á, Camporez JP, Suárez Y, Rodeheffer MS, Shulman GI, de Cabo R, Fernández-Hernando C. Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance. Cell Reports 2018, 22: 2133-2145. PMID: 29466739, PMCID: PMC5860817, DOI: 10.1016/j.celrep.2018.01.074.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAdiposityAnimalsCholesterol, HDLCholesterol, LDLEatingEnzyme ActivationGene DeletionGene Expression RegulationGenetic Predisposition to DiseaseGerm CellsInflammation MediatorsInsulin ResistanceLipid MetabolismLiverMice, Inbred C57BLMicroRNAsModels, BiologicalObesityProtein Kinase C-epsilonSterol Regulatory Element Binding Protein 1ConceptsMiR-33Insulin resistanceFood intakeIncreases food intakeAdipose tissue expansionKey metabolic tissuesWild-type animalsPromotes obesityImpaired lipolysisPair feedingCardiovascular diseaseMetabolic dysfunctionTherapeutic modulationAdipose tissueLipid uptakeMiRNA-based therapiesMetabolic tissuesGenetic ablationTissue expansionMiceObesityTherapyDeleterious effectsDiseasePrevious reports
2017
Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins
Singh AK, Aryal B, Zhang X, Fan Y, Price NL, Suárez Y, Fernández-Hernando C. Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins. Seminars In Cell And Developmental Biology 2017, 81: 129-140. PMID: 29183708, PMCID: PMC5975105, DOI: 10.1016/j.semcdb.2017.11.026.Peer-Reviewed Original ResearchConceptsLipid metabolismNon-coding RNAImportance of microRNAsNumber of miRNAsRole of lncRNAsLipid-related genesTranscriptional regulationCoding RNAsPosttranscriptional regulationPosttranscriptional levelMiRNA expressionHigh abundanceLncRNAsRNACholesterol homeostasisMiR-33MiR-148aSpecific roleMiRNAsRegulationLipoprotein metabolismRecent findingsMetabolismProteinExpression
2016
Preface to: “microRNAs in lipid/energy metabolism and cardiometabolic disease”
Suárez Y, Fernández-Hernando C. Preface to: “microRNAs in lipid/energy metabolism and cardiometabolic disease”. Biochimica Et Biophysica Acta 2016, 1861: 2039-2040. PMID: 27396679, DOI: 10.1016/j.bbalip.2016.07.001.Commentaries, Editorials and LettersAkt‐mediated foxo1 inhibition is required for liver regeneration
Pauta M, Rotllan N, Fernández-Hernando A, Langhi C, Ribera J, Lu M, Boix L, Bruix J, Jimenez W, Suárez Y, Ford DA, Baldán A, Birnbaum MJ, Morales-Ruiz M, Fernández-Hernando C. Akt‐mediated foxo1 inhibition is required for liver regeneration. Hepatology 2016, 63: 1660-1674. PMID: 26473496, PMCID: PMC5177729, DOI: 10.1002/hep.28286.Peer-Reviewed Original ResearchConceptsAkt/protein kinase BCellular eventsProtein kinase BAkt2-deficient miceAbsence of Akt1Lipid droplet formationContribution of AktAkt2-null miceLiver regenerationAbnormal cellular eventsTranscription factorsAKT-FOXO1Kinase BLiver-specific deletionSuccessful liver regenerationPartial hepatectomyHepatic regenerative capabilityAKT1Chronic liver diseaseFOXO1 inhibitionCell proliferationEssential roleImpaired liver regenerationIntracellular mediatorsEfficient liver regenerationMicroRNAs as regulators of endothelial cell functions in cardiometabolic diseases
Araldi E, Suárez Y. MicroRNAs as regulators of endothelial cell functions in cardiometabolic diseases. Biochimica Et Biophysica Acta 2016, 1861: 2094-2103. PMID: 26825686, PMCID: PMC5039046, DOI: 10.1016/j.bbalip.2016.01.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndothelial CellsEndothelium, VascularHeart DiseasesHumansLipid MetabolismMetabolic DiseasesMicroRNAsConceptsSmall non-coding RNAsLipid/energy metabolismCarlos Fernández-HernandoRegulation of ECNon-coding RNAsRole of miRNAsEndothelial cellsYajaira SuárezTissue homeostasisCell deathEndothelial cell functionEnvironmental stimuliEnergy metabolismMicroRNAsCell proliferationImportant functionsPotential therapeutic applicationsCell functionMiRNAsDifferent cardiometabolic diseasesMetabolic imbalanceEC dysfunctionTherapeutic applicationsPresent reviewRelated diseases
2014
Long‐term therapeutic silencing of miR‐33 increases circulating triglyceride levels and hepatic lipid accumulation in mice
Goedeke L, Salerno A, Ramírez CM, Guo L, Allen RM, Yin X, Langley SR, Esau C, Wanschel A, Fisher EA, Suárez Y, Baldán A, Mayr M, Fernández-Hernando C. Long‐term therapeutic silencing of miR‐33 increases circulating triglyceride levels and hepatic lipid accumulation in mice. EMBO Molecular Medicine 2014, 6: 1133-1141. PMID: 25038053, PMCID: PMC4197861, DOI: 10.15252/emmm.201404046.Peer-Reviewed Original ResearchConceptsHigh-fat dietFatty acid synthaseMiR-33Chronic inhibitionTriglyceride levelsTherapeutic silencingHigh-density lipoprotein levelsAcetyl-CoA carboxylaseLipid accumulationAtherosclerotic vascular diseaseHepatic lipid accumulationRegression of atherosclerosisModerate hepatic steatosisLiver of miceNon-human primatesLipoprotein levelsHepatic steatosisVascular diseaseLong-term effectsStrong inverse correlationPersistent inhibitionVivo increaseCholesterol transportMiceAdverse effects
2013
A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression
Goedeke L, Vales-Lara FM, Fenstermaker M, Cirera-Salinas D, Chamorro-Jorganes A, Ramírez CM, Mattison JA, de Cabo R, Suárez Y, Fernández-Hernando C. A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression. Molecular And Cellular Biology 2013, 33: 2339-2352. PMID: 23547260, PMCID: PMC3648071, DOI: 10.1128/mcb.01714-12.Peer-Reviewed Original ResearchConceptsMiR-33Gene expressionRegulatory roleTarget gene networkKey transcriptional regulatorTarget gene expressionMetabolism gene expressionIntronic microRNAsHuman hepatic cellsLipid metabolismSterol regulatory element-binding protein 2Transcriptional regulatorsSister strandsGene networksLipid metabolism gene expressionSteady-state levelsHost genesFatty acid metabolismFatty acid oxidationKey enzymeLipid homeostasisPassenger strandMicroRNA-33Functional roleProtein 2MicroRNAs in Metabolic Disease
Fernández-Hernando C, Ramírez CM, Goedeke L, Suárez Y. MicroRNAs in Metabolic Disease. Arteriosclerosis Thrombosis And Vascular Biology 2013, 33: 178-185. PMID: 23325474, PMCID: PMC3740757, DOI: 10.1161/atvbaha.112.300144.BooksConceptsContribution of miRNAsCellular cholesterol exportMiR-33Fatty acid degradationSREBP genesIntronic miRNAMetabolic diseasesFatty acid synthesisHost genesCholesterol exportSpecific miRNAsPhysiological processesLipid homeostasisMiRNAsAcid synthesisAcid degradationCardiometabolic diseasesGenesMicroRNAsGlucose homeostasisCritical roleGlucose metabolismLipoprotein secretionRecent findingsMetabolic control
2011
MicroRNA-758 Regulates Cholesterol Efflux Through Posttranscriptional Repression of ATP-Binding Cassette Transporter A1
Ramirez CM, Dávalos A, Goedeke L, Salerno AG, Warrier N, Cirera-Salinas D, Suárez Y, Fernández-Hernando C. MicroRNA-758 Regulates Cholesterol Efflux Through Posttranscriptional Repression of ATP-Binding Cassette Transporter A1. Arteriosclerosis Thrombosis And Vascular Biology 2011, 31: 2707-2714. PMID: 21885853, PMCID: PMC3298756, DOI: 10.1161/atvbaha.111.232066.Peer-Reviewed Original ResearchConceptsATP-binding cassette transporter A1Cassette transporter A1Posttranscriptional regulationCellular cholesterol effluxUnbiased genome-wide screenMiR-758Cholesterol effluxGenome-wide screenExpression of ABCA1Cholesterol-loaded macrophagesIntracellular cholesterol accumulationPosttranscriptional repressionNovel miRNABioinformatics analysisMouse cellsMajor regulatorHuman cellsLuciferase reporterMacrophage cholesterol effluxMouse peritoneal macrophagesPeritoneal macrophagesABCA1 geneABCA1 expressionQuantitative real-time reverse transcription-polymerase chain reactionHigh-density lipoprotein levelsThe Role of MicroRNAs in Cholesterol Efflux and Hepatic Lipid Metabolism
Moore KJ, Rayner KJ, Suárez Y, Fernández-Hernando C. The Role of MicroRNAs in Cholesterol Efflux and Hepatic Lipid Metabolism. Annual Review Of Nutrition 2011, 31: 49-63. PMID: 21548778, PMCID: PMC3612434, DOI: 10.1146/annurev-nutr-081810-160756.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsCardiovascular DiseasesCholesterolFatty AcidsHumansLipid MetabolismLipoproteins, HDLLiverMicroRNAsConceptsGene expressionSterol response element-binding proteinMiR-33Fatty acid β-oxidationElement-binding proteinFatty acid homeostasisResponse element-binding proteinRole of microRNAsCholesterol effluxIntronic miRNALipid metabolismRNA bindsPosttranscriptional controlUntranslated regionAbundant miRNABiological processesElegant mechanismMiR-122Lipid homeostasisΒ-oxidationAcid homeostasisCell phenotypeMiRNAsHepatic lipid metabolismMicroRNAsAntagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis
Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, van Gils JM, Rayner AJ, Chang AN, Suarez Y, Fernandez-Hernando C, Fisher EA, Moore KJ. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. Journal Of Clinical Investigation 2011, 121: 2921-2931. PMID: 21646721, PMCID: PMC3223840, DOI: 10.1172/jci57275.Peer-Reviewed Original ResearchConceptsABC transporter A1HDL levelsRegression of atherosclerosisCholesterol transportMiR-33MiR-33 inhibitionAtherosclerotic vascular diseasePlasma HDL levelsInflammatory gene expressionReverse cholesterol transportABCA1 levelsAtherosclerosis regressionVascular diseasePlaque macrophagesPlaque stabilityABCA1 expressionAtherosclerotic plaquesMice promotesProtective roleLipid metabolismLDL receptorClinical therapyPlaque sizeAtherosclerosisSREBF2 geneMicroRNAs in lipid metabolism
Fernández-Hernando C, Suárez Y, Rayner KJ, Moore KJ. MicroRNAs in lipid metabolism. Current Opinion In Lipidology 2011, 22: 86-92. PMID: 21178770, PMCID: PMC3096067, DOI: 10.1097/mol.0b013e3283428d9d.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCholesterolFatty AcidsHumansLipid MetabolismMicroRNAsSterol Regulatory Element Binding ProteinsConceptsFatty acid metabolismPotent post-transcriptional regulatorsLipid metabolismPost-transcriptional regulatorsCholesterol homeostasisMiR-33Multiple physiological processesAcid metabolismFatty acid degradationFatty acid β-oxidationLipid metabolism genesTiny RNAsTranscriptional regulationABC transportersMetabolism genesFatty acid oxidationHDL biogenesisPhysiological processesCell differentiationMiR-27MiRNAsΒ-oxidationMiR-335Cellular levelMiR-370
2010
microRNAs and cholesterol metabolism
Moore KJ, Rayner KJ, Suárez Y, Fernández-Hernando C. microRNAs and cholesterol metabolism. Trends In Endocrinology And Metabolism 2010, 21: 699-706. PMID: 20880716, PMCID: PMC2991595, DOI: 10.1016/j.tem.2010.08.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP-Binding Cassette TransportersCholesterolHumansLipid MetabolismMicroRNAsModels, BiologicalConceptsPotent post-transcriptional regulatorsPost-transcriptional regulatorsMiR-33Non-coding RNALipid metabolism genesCholesterol metabolismTranscriptional regulationEpigenetic regulationFatty acid metabolismABC transportersMetabolism genesHDL biogenesisCellular levelCholesterol homeostasisMicroRNAsAcid metabolismImportant roleMiR-370Cholesterol effluxMetabolismMiR-122RegulationNew avenuesBiogenesisGenes