2024
miR-33 deletion in hepatocytes attenuates NAFLD-NASH-HCC progression
Fernández-Tussy P, Cardelo M, Zhang H, Sun J, Price N, Boutagy N, Goedeke L, Cadena-Sandoval M, Xirouchaki C, Brown W, Yang X, Pastor-Rojo O, Haeusler R, Bennett A, Tiganis T, Suárez Y, Fernández-Hernando C. miR-33 deletion in hepatocytes attenuates NAFLD-NASH-HCC progression. JCI Insight 2024, 9: e168476. PMID: 39190492, PMCID: PMC11466198, DOI: 10.1172/jci.insight.168476.Peer-Reviewed Original ResearchMiR-33Regulation of biological processesMitochondrial fatty acid oxidationRegulation of lipid metabolismNon-alcoholic fatty liver diseaseDevelopment of effective therapeuticsFatty acid oxidationLipid synthesisProgression of non-alcoholic fatty liver diseaseMitochondrial functionTarget genesBiological processesComplex diseasesNon-alcoholic steatohepatitisLipid accumulationDeletionDevelopment of non-alcoholic fatty liver diseasePathway activationLipid metabolismProgress to non-alcoholic steatohepatitisAcid oxidationHCC progressionEffective therapeuticsTherapeutic targetHepatocellular carcinomamicroRNA-33 controls hunger signaling in hypothalamic AgRP neurons
Price N, Fernández-Tussy P, Varela L, Cardelo M, Shanabrough M, Aryal B, de Cabo R, Suárez Y, Horvath T, Fernández-Hernando C. microRNA-33 controls hunger signaling in hypothalamic AgRP neurons. Nature Communications 2024, 15: 2131. PMID: 38459068, PMCID: PMC10923783, DOI: 10.1038/s41467-024-46427-0.Peer-Reviewed Original ResearchConceptsAgRP neuronsFeeding behaviorFatty acid metabolismNon-coding RNAsMitochondrial biogenesisRegulatory pathwaysTarget genesHypothalamic AgRP neuronsExcessive nutrient intakeCentral regulatorBioenergetic processesAcid metabolismActivation of AgRP neuronsModulate feeding behaviorCentral regulation of feeding behaviorRegulation of feeding behaviorMiR-33Hunger signalsMicroRNA-33Metabolic diseasesAlternative therapeutic approachLoss of miR-33Mouse modelMetabolic dysfunctionRegulation
2022
Targeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression
Zhang X, Rotllan N, Canfrán-Duque A, Sun J, Toczek J, Moshnikova A, Malik S, Price NL, Araldi E, Zhong W, Sadeghi MM, Andreev OA, Bahal R, Reshetnyak YK, Suárez Y, Fernández-Hernando C. Targeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression. Circulation Research 2022, 131: 77-90. PMID: 35534923, PMCID: PMC9640270, DOI: 10.1161/circresaha.121.320296.Peer-Reviewed Original ResearchConceptsMiR-33Gene expressionNature of miRNAsSingle-cell RNA sequencing analysisSingle-cell RNA transcriptomicsAnti-miRNA technologiesRNA sequencing analysisExpression of miRNAsRNA transcriptomicsNew therapeutic opportunitiesEntire pathwayMiRNA therapeuticsAtherosclerotic plaque macrophagesHuman diseasesMiRNAsSequencing analysisSpecific tissuesMetabolic tissuesTargeted suppressionMiR-33 inhibitionProtective miRNAsNumerous diseasesPharmacological inhibitionLipid accumulationTarget effects
2021
Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis
Price NL, Zhang X, Fernández-Tussy P, Singh AK, Burnap SA, Rotllan N, Goedeke L, Sun J, Canfrán-Duque A, Aryal B, Mayr M, Suárez Y, Fernández-Hernando C. Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2006478118. PMID: 33495342, PMCID: PMC7865172, DOI: 10.1073/pnas.2006478118.Peer-Reviewed Original ResearchConceptsMiR-33 deficiencyHDL-C levelsMiR-33Body weightAtherosclerotic plaque sizeAtherosclerotic plaque burdenDevelopment of fibrosisCholesterol transport capacityCholesterol transporter ABCA1High-density lipoprotein biogenesisSREBP2 transcription factorKnockout mouse modelConditional knockout mouse modelPlaque burdenCardiometabolic diseasesChow dietLiver functionMetabolic dysfunctionHDL metabolismHyperlipidemic conditionsMouse modelGlucose homeostasisCholesterol effluxLipid metabolismObesity
2019
Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis
Price NL, Miguel V, Ding W, Singh AK, Malik S, Rotllan N, Moshnikova A, Toczek J, Zeiss C, Sadeghi MM, Arias N, Baldán Á, Andreev OA, Rodríguez-Puyol D, Bahal R, Reshetnyak YK, Suárez Y, Fernández-Hernando C, Lamas S. Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis. JCI Insight 2019, 4 PMID: 31613798, PMCID: PMC6948871, DOI: 10.1172/jci.insight.131102.Peer-Reviewed Original ResearchConceptsFatty acid oxidationChronic kidney diseaseKidney diseaseDisease progressionMiR-33Bone marrow transplantExtent of fibrosisDevelopment of fibrosisAttractive therapeutic targetExpression of factorsNucleic acid inhibitorsMarrow transplantKidney fibrosisFibrotic kidneysMouse modelTherapeutic targetLipid metabolismPharmacological inhibitionFibrosisLipid accumulationDiseaseGenetic deficiencyProgressionKidneyAcid oxidationSpecific Disruption of Abca1 Targeting Largely Mimics the Effects of miR-33 Knockout on Macrophage Cholesterol Efflux and Atherosclerotic Plaque Development
Price NL, Rotllan N, Zhang X, Canfrán-Duque A, Nottoli T, Suarez Y, Fernández-Hernando C. Specific Disruption of Abca1 Targeting Largely Mimics the Effects of miR-33 Knockout on Macrophage Cholesterol Efflux and Atherosclerotic Plaque Development. Circulation Research 2019, 124: 874-880. PMID: 30707082, PMCID: PMC6417928, DOI: 10.1161/circresaha.118.314415.Peer-Reviewed Original ResearchConceptsMacrophage cholesterol effluxAtherosclerotic plaque formationCholesterol effluxMiR-33Proatherogenic effectsABCA1 expressionBone marrowDeficient animalsPlaque formationMiR-33-deficient miceHigh-fat diet feedingHepatic ABCA1 expressionAtherosclerotic plaque burdenFat diet feedingDevelopment of obesityNovel mouse modelAtherosclerotic plaque developmentFoam cell formationPlaque burdenDeficient miceDiet feedingMetabolic dysfunctionSpecific disruptionMouse modelKnockout mice
2018
Genetic 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 findingsMetabolismProteinExpressionGenetic Dissection of the Impact of miR-33a and miR-33b during the Progression of Atherosclerosis
Price NL, Rotllan N, Canfrán-Duque A, Zhang X, Pati P, Arias N, Moen J, Mayr M, Ford DA, Baldán Á, Suárez Y, Fernández-Hernando C. Genetic Dissection of the Impact of miR-33a and miR-33b during the Progression of Atherosclerosis. Cell Reports 2017, 21: 1317-1330. PMID: 29091769, PMCID: PMC5687841, DOI: 10.1016/j.celrep.2017.10.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAtherosclerosisATP Binding Cassette Transporter 1Blood GlucoseCells, CulturedCholesterolCholesterol, HDLDisease ProgressionGene Regulatory NetworksMacrophages, PeritonealMaleMiceMice, Inbred C57BLMice, KnockoutMicroRNAsMitochondrial Trifunctional Protein, beta SubunitMyocardiumReceptors, LDLConceptsPlaque burdenMiR-33MiR-33-deficient miceReduced plaque burdenProgression of atherosclerosisPro-atherogenic effectsMacrophage cholesterol effluxDecreases lipid accumulationTreatment of atherosclerosisMacrophage-specific lossMiR-33 deficiencyPromotes obesityHDL levelsInsulin resistancePlaque macrophagesProtective effectHyperlipidemic conditionsCholesterol effluxPlaque developmentLipid metabolismAtherosclerosisLipid accumulationHDL biogenesisPromising targetMacrophages
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
2012
Mir-33 regulates cell proliferation and cell cycle progression
Cirera-Salinas D, Pauta M, Allen RM, Salerno AG, Ramírez CM, Chamorro-Jorganes A, Wanschel AC, Lasuncion MA, Morales-Ruiz M, Suarez Y, Baldan A, Esplugues E, Fernández-Hernando C. Mir-33 regulates cell proliferation and cell cycle progression. Cell Cycle 2012, 11: 922-933. PMID: 22333591, PMCID: PMC3323796, DOI: 10.4161/cc.11.5.19421.Peer-Reviewed Original ResearchConceptsCell cycle progressionCyclin-dependent kinase 6Cycle progressionCell proliferationCell cycle regulationMiR-33Expression of genesCyclin D1Cell cycle arrestSREBP genesCycle regulationFatty acid metabolismHost genesPosttranscriptional levelGene expressionIntronic sequencesKinase 6Cellular growthCritical regulatorCycle arrestCellular levelLiver regenerationGenesMiR-33 expressionAcid metabolism
2011
The 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 ResearchConceptsGene 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 ResearchConceptsFatty 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 ResearchConceptsPotent 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 avenuesBiogenesisGenesMiR-33 Contributes to the Regulation of Cholesterol Homeostasis
Rayner KJ, Suárez Y, Dávalos A, Parathath S, Fitzgerald ML, Tamehiro N, Fisher EA, Moore KJ, Fernández-Hernando C. MiR-33 Contributes to the Regulation of Cholesterol Homeostasis. Science 2010, 328: 1570-1573. PMID: 20466885, PMCID: PMC3114628, DOI: 10.1126/science.1189862.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoprotein A-IATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily G, Member 1ATP-Binding Cassette TransportersCarrier ProteinsCell LineCholesterolCholesterol, DietaryDietary FatsGene Expression RegulationHomeostasisHumansHypercholesterolemiaIntracellular Signaling Peptides and ProteinsIntronsLipoproteinsLipoproteins, HDLLiverMacrophagesMacrophages, PeritonealMembrane GlycoproteinsMiceMice, Inbred C57BLMicroRNAsNiemann-Pick C1 ProteinProteinsSterol Regulatory Element Binding Protein 2TransfectionConceptsSterol regulatory element-binding factor-2MiR-33Cellular cholesterol transportCholesterol effluxExpression of genesIntronic microRNAsTranscriptional regulatorsTriphosphate-binding cassette transportersAdenosine triphosphate-binding cassette transportersCellular cholesterol effluxCassette transportersHDL biogenesisHuman cellsCellular levelCholesterol homeostasisABCA1 expressionFactor 2Mouse macrophagesGenesLentiviral deliveryCholesterol transportExpressionABCA1Cholesterol metabolismEfflux