2021
MMAB promotes negative feedback control of cholesterol homeostasis
Goedeke L, Canfrán-Duque A, Rotllan N, Chaube B, Thompson BM, Lee RG, Cline GW, McDonald JG, Shulman GI, Lasunción MA, Suárez Y, Fernández-Hernando C. MMAB promotes negative feedback control of cholesterol homeostasis. Nature Communications 2021, 12: 6448. PMID: 34750386, PMCID: PMC8575900, DOI: 10.1038/s41467-021-26787-7.Peer-Reviewed Original ResearchMeSH KeywordsAlkyl and Aryl TransferasesAnimalsCell Line, TumorCholesterolCholesterol, LDLFeedback, PhysiologicalGene Expression ProfilingHeLa CellsHep G2 CellsHomeostasisHumansHydroxymethylglutaryl CoA ReductasesLiverMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticReceptors, LDLRNA InterferenceSterol Regulatory Element Binding Protein 2ConceptsCholesterol biosynthesisCholesterol homeostasisMouse hepatic cell lineIntegrative genomic strategyIntricate regulatory networkMaster transcriptional regulatorCellular cholesterol levelsHMGCR activityLDL-cholesterol uptakeCholesterol levelsHuman hepatic cellsSterol contentGenomic strategiesTranscriptional regulatorsRegulatory networksIntracellular cholesterol levelsGene expressionUnexpected roleHepatic cell linesBiosynthesisMMABIntracellular levelsCell linesHomeostasisExpression of SREBP2
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
2015
MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels
Goedeke L, Rotllan N, Canfrán-Duque A, Aranda JF, Ramírez CM, Araldi E, Lin CS, Anderson NN, Wagschal A, de Cabo R, Horton JD, Lasunción MA, Näär AM, Suárez Y, Fernández-Hernando C. MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels. Nature Medicine 2015, 21: 1280-1289. PMID: 26437365, PMCID: PMC4711995, DOI: 10.1038/nm.3949.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter 1Cholesterol, HDLCholesterol, LDLGene Expression RegulationHep G2 CellsHepatocytesHigh-Throughput Screening AssaysHumansLiverMiceMicroRNAsReceptors, LDLRNA Processing, Post-TranscriptionalSignal TransductionSterol Regulatory Element Binding Protein 1
2009
Nogo-B Receptor Stabilizes Niemann-Pick Type C2 Protein and Regulates Intracellular Cholesterol Trafficking
Harrison KD, Miao RQ, Fernandez-Hernándo C, Suárez Y, Dávalos A, Sessa WC. Nogo-B Receptor Stabilizes Niemann-Pick Type C2 Protein and Regulates Intracellular Cholesterol Trafficking. Cell Metabolism 2009, 10: 208-218. PMID: 19723497, PMCID: PMC2739452, DOI: 10.1016/j.cmet.2009.07.003.Peer-Reviewed Original ResearchConceptsNiemann-Pick type C2 (NPC2) proteinIntracellular cholesterol traffickingC2 proteinCholesterol traffickingEndoplasmic reticulumTwo-hybrid screenC-terminal domainCellular rolesIntracellular cholesterol accumulationSterol sensingProtein stabilityN-terminusNgBRProteinProtein levelsNPC2 mutationsCholesterol accumulationGenetic deficiencyTraffickingRNAiNPC2TerminusBiologyBaitReticulumGenetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of Atherosclerosis
Fernández-Hernando C, Yu J, Suárez Y, Rahner C, Dávalos A, Lasunción MA, Sessa WC. Genetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of Atherosclerosis. Cell Metabolism 2009, 10: 48-54. PMID: 19583953, PMCID: PMC2735117, DOI: 10.1016/j.cmet.2009.06.003.Peer-Reviewed Original ResearchConceptsProgression of atherosclerosisInitiation of atherosclerosisCav-1ApoE knockout backgroundArtery wallKnockout backgroundLeukocyte adhesion moleculesNitric oxide productionEndothelial Cav-1 expressionCav-1 expressionEndothelial caveolin-1AtherosclerosisTransgenic miceOxide productionGenetic ablationLDL infiltrationAdhesion moleculesCritical roleCaveolin-1 geneLDL-derived cholesterolMiceVessel wallPhysiological evidenceLesion expansionGenetic evidence
2004
Synergistic upregulation of low-density lipoprotein receptor activity by tamoxifen and lovastatin
Suárez Y, Fernández C, Gómez-Coronado D, Ferruelo AJ, Dávalos A, Martínez-Botas J, Lasunción MA. Synergistic upregulation of low-density lipoprotein receptor activity by tamoxifen and lovastatin. Cardiovascular Research 2004, 64: 346-355. PMID: 15485695, DOI: 10.1016/j.cardiores.2004.06.024.Peer-Reviewed Original ResearchConceptsLDL receptor activityLow-density lipoproteinReceptor activityLow density lipoprotein receptor activityPlasma LDL cholesterol levelsLDL cholesterol levelsLipoprotein receptor activityEstrogen receptor modulatorsBreast cancer therapyReceptor mRNA levelsLDL receptor mRNA levelsLDL receptor expressionCholesterol-lowering activityDose-dependent mannerHigh LDL concentrationsHypolipidemic effectsMOLT-4 cellsCholesterol levelsReceptor expressionReceptor modulatorsEstrogen receptorTamoxifenLDL concentrationLDL uptakeLDL receptor
2002
A double mutant [N543H+2393del9] allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease
Castillo S, Reyes G, Tejedor D, Mozas P, Suarez Y, Lasuncion M, Cenarro A, Civeira F, Alonso R, Mata P, Pocovi M, Group of FH O. A double mutant [N543H+2393del9] allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease. Human Mutation 2002, 20: 477-477. PMID: 12442279, DOI: 10.1002/humu.9087.Peer-Reviewed Original ResearchConceptsDouble mutant alleleLDL receptor geneFamilial hypercholesterolemiaHomozygous patientsReceptor geneSpanish FH patientsCholesterol-lowering treatmentLDL cholesterol reductionPlasma cholesterol levelsAbility of LDLMitogen-stimulated lymphocytesCholesterol levelsCholesterol reductionFH patientsCardiovascular diseasePatientsHomozygous FHHeterozygous patientsUnrelated patientsCytometric analysisHypercholesterolemiaLDL bindingDefective LDL bindingCell proliferationGenetic disorders
2001
Dose-dependent effects of lovastatin on cell cycle progression. Distinct requirement of cholesterol and non-sterol mevalonate derivatives
Martı́nez-Botas J, Ferruelo A, Suárez Y, Fernández C, Gómez-Coronado D, Lasunción M. Dose-dependent effects of lovastatin on cell cycle progression. Distinct requirement of cholesterol and non-sterol mevalonate derivatives. Biochimica Et Biophysica Acta 2001, 1532: 185-194. PMID: 11470239, DOI: 10.1016/s1388-1981(01)00125-1.Peer-Reviewed Original ResearchConceptsCell proliferationLow-density lipoprotein cholesterolCell cycle progressionDose-dependent effectCell cycle distributionCell cycleCycle progressionLipoprotein cholesterolConcentrations of lovastatinCholesterol supplyCycle distributionCholesterolLovastatinHuman cell linesCell linesCholesterol biosynthesisCholesterol-free mediumNormal cell cyclingM phaseProgressionProliferationPresent studyHL-60Mevalonate derivativesCell cycling