2013
Rare Nonconservative LRP6 Mutations Are Associated with Metabolic Syndrome
Singh R, Smith E, Fathzadeh M, Liu W, Go G, Subrahmanyan L, Faramarzi S, McKenna W, Mani A. Rare Nonconservative LRP6 Mutations Are Associated with Metabolic Syndrome. Human Mutation 2013, 34: 1221-1225. PMID: 23703864, PMCID: PMC3745535, DOI: 10.1002/humu.22360.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCase-Control StudiesCoronary DiseaseEuropeFemaleGenetic Predisposition to DiseaseGenetic VariationGlycosylationHumansLow Density Lipoprotein Receptor-Related Protein-6MaleMetabolic SyndromeMiddle AgedMutationPedigreePhylogenySequence AlignmentUnited StatesWnt ProteinsYoung AdultConceptsCoronary artery diseaseMetabolic syndromeLRP6 mutationFamilial coronary artery diseaseArtery diseaseDisease populationSyndromeConserved glycosylation siteNovel mutationsFunction mutationsPropeller domainRare mutationsEuropean controlsLRP6MutationsCritical roleMetabolic traitsWhite AmericansPrevalenceDisease
2012
Low Density Lipoprotein (LDL) Receptor-related Protein 6 (LRP6) Regulates Body Fat and Glucose Homeostasis by Modulating Nutrient Sensing Pathways and Mitochondrial Energy Expenditure*
Liu W, Singh R, Choi CS, Lee HY, Keramati AR, Samuel VT, Lifton RP, Shulman GI, Mani A. Low Density Lipoprotein (LDL) Receptor-related Protein 6 (LRP6) Regulates Body Fat and Glucose Homeostasis by Modulating Nutrient Sensing Pathways and Mitochondrial Energy Expenditure*. Journal Of Biological Chemistry 2012, 287: 7213-7223. PMID: 22232553, PMCID: PMC3293520, DOI: 10.1074/jbc.m111.286724.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, BrownAdiposityAllelesAnimalsDiabetes Mellitus, Type 2Dietary FatsEnergy MetabolismForkhead Box Protein O1Forkhead Transcription FactorsGluconeogenesisGlucoseGlucose-6-PhosphataseHomeostasisInsulin ResistanceLow Density Lipoprotein Receptor-Related Protein-6Mechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMitochondriaMultiprotein ComplexesObesityProteinsReceptors, LeptinTOR Serine-Threonine KinasesWnt Signaling PathwayConceptsLow-density lipoprotein receptor-related protein 6Type 2 diabetesInsulin resistanceInsulin sensitivityBody fatAdipose tissue insulin sensitivityLipoprotein receptor-related protein 6Tissue insulin resistanceTissue insulin sensitivityDiet-induced obesityHigh-fat dietLeptin receptor expressionHepatic insulin sensitivityHepatic glucose outputWild-type littermatesFoxo1-dependent expressionMitochondrial energy expenditureMetabolic syndromeFat dietReduced adiposityReceptor expressionPharmacological interventionsGlucose outputGlucose homeostasisKey gluconeogenic enzymes
2011
LRP6 Protein Regulates Low Density Lipoprotein (LDL) Receptor-mediated LDL Uptake*
Ye ZJ, Go GW, Singh R, Liu W, Keramati AR, Mani A. LRP6 Protein Regulates Low Density Lipoprotein (LDL) Receptor-mediated LDL Uptake*. Journal Of Biological Chemistry 2011, 287: 1335-1344. PMID: 22128165, PMCID: PMC3256876, DOI: 10.1074/jbc.m111.295287.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SubstitutionAnimalsCHO CellsClathrinCricetinaeCricetulusEndocytosisFibroblastsGene Knockdown TechniquesHumansLipoproteins, LDLLow Density Lipoprotein Receptor-Related Protein-6Mutation, MissenseReceptors, LDLConceptsLDL uptakeLDL bindingHigh serum LDL cholesterol levelReceptor-mediated LDL uptakeSerum LDL cholesterol levelsSerum LDL levelsHigh serum LDL levelsLDL cholesterol levelsPeripheral B lymphocytesLDL levelsCholesterol levelsLDL clearanceLRP6 knockdownMutation carriersImpaired functionB lymphocytesLDL receptorLRP6 geneCHO cellsCritical modulatorLDLRLDL endocytosisGreater declineCHO-K1 cellsLRP6
2008
Mutation in EGFP Domain of LDL Receptor-Related Protein 6 Impairs Cellular LDL Clearance
Liu W, Mani S, Davis NR, Sarrafzadegan N, Kavathas PB, Mani A. Mutation in EGFP Domain of LDL Receptor-Related Protein 6 Impairs Cellular LDL Clearance. Circulation Research 2008, 103: 1280-1288. PMID: 18948618, PMCID: PMC3426315, DOI: 10.1161/circresaha.108.183863.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SubstitutionAnimalsApolipoproteins BB-LymphocytesCell LineCell MembraneEndosomesGene Expression RegulationGenetic Carrier ScreeningGreen Fluorescent ProteinsHumansImmunohistochemistryLDL-Receptor Related ProteinsLipoproteins, LDLLow Density Lipoprotein Receptor-Related Protein-6LysosomesMetabolic Clearance RateMiceMice, KnockoutMicroscopy, FluorescenceMutationConceptsLDL clearanceMutation carriersWild-type receptorEarly-onset atherosclerosisLow-density lipoprotein uptakeWild-type littermatesLymphoblastoid cellsSplenic B cellsTotal LRP6LDL receptor-related protein 6Unaffected family membersApolipoprotein BLRP6 expressionMembrane expression levelsB cellsLipoprotein uptakeLDL uptakeCholesterol uptakeLDL receptorLow efficacyPlasma membrane expression levelsReceptorsLDL endocytosisMembrane expressionProtein 6