课题基金 / 基金详情

The role of LPCAT3 in pathogenesis of diabetic cardiomyopathy

The role of LPCAT3 in pathogenesis of diabetic cardiomyopathy
LPCAT3在糖尿病心肌病发病机制中的作用
批准号:
10867671
负责人:
Tomasz Krzysztof Bednarski
金额:
$15.27万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-06-01 至 2025-05-31
关键词:
ATF6 geneAcuteAcyltransferaseAffectAgeAnimal ExperimentsAnimalsAntibodiesApoptosisAreaBiological AssayBloodBody CompositionBody WeightC57BL/6 MouseCD36 geneCardiacCardiac MyocytesCardiovascular DiseasesCaspaseCause of DeathCaymansCd68Cell LineCell ProliferationCell SurvivalCellsCeramidesChemicalsCholesterolCholesterol EstersCollaborationsComputer softwareContractsControl GroupsCustomCytomegalovirusDependovirusDevelopmentDiabetes MellitusDietDiet ResearchDiglyceridesDiseaseDoseDyslipidemiasEatingEnsureEnzymesEvaluationFastingFat-Restricted DietFatty acid glycerol estersFelis catusFutureGCG geneGRP78 geneGRP94Gene ExpressionGenotypeGenus HippocampusGlucoseGlucose tolerance testGlutamineGlycolysisHeart AbnormalitiesHeart failureHigh Fat DietHourHypertensionITGAM geneImageIncubatedIndividualInflammationInjectionsInsulinInsulin ResistanceInterleukin-4Interleukin-6Intraperitoneal InjectionsKnock-outKnockout MiceKnowledgeLaboratoriesLecithinLipid PeroxidationLipidsLipolysisLiverLiver X ReceptorLoxP-flanked alleleLysophosphatidylcholinesMass FragmentographyMeasuresMembraneMetabolicMetabolic DiseasesMetabolic PathwayMetabolismMicroscopeMitochondriaMolecularMonitorMusMyocardial dysfunctionMyosin Heavy ChainsNebraskaNon-Insulin-Dependent Diabetes MellitusNonesterified Fatty AcidsObese MiceObesityOilsOxidative PhosphorylationOxidative StressOxygen ConsumptionPalmitatesPancreasPathogenesisPatientsPharmacotherapyPhenotypePhospholipidsPhosphorylationPhysiologyPlasmaPlayPolyunsaturated Fatty AcidsPositioning AttributePrevention strategyProductionPromegaProteinsRNA SplicingReactive Oxygen SpeciesReceptor ActivationRespirationRisk FactorsRoleSOD2 geneSignal TransductionStainsStreptozocinStructureSupplementationSystemTNF geneTestingThe Jackson LaboratoryThiobarbituric Acid Reactive SubstancesTissuesTobacco useTransforming Growth Factor alphaUniversitiesUnsaturated Fatty AcidsVentricular Cardiac alpha-MyosinWestern BlottingWomanXBP1 genealpha Actinincontinuous cell linedb/db mousediabeticdiabetic cardiomyopathydiagnostic tooldietarydigitalendoplasmic reticulum stressexperimental groupexperimental studyextracellularfatty acid oxidationfeedingheart functionheart metabolismimprovedin vivoinsulin sensitivitylipid biosynthesislipidomelong chain fatty acidmalemennano-stringobesity preventionoverexpressionoxidationoxidative DNA damagepreventstandard measuresuperoxide dismutase 1transcription factortransduction efficiency

项目摘要

项目成果

相似基金

相关文献

中文摘要
翻译
心血管疾病是全球头号死亡原因。大多数心血管疾病是由风险引起的
英文摘要
Cardiovascular diseases are the number one cause of death globally. Most CVDs are caused by risk factors such as tobacco use, hypertension, obesity or diabetes. Diabetic cardiomyopathy (DC) is characterized by abnormal cardiac structure and function in the absence of other cardiac risk factors and is often undiagnosed in patients with diabetes mellitus. Untreated, this condition increases the chance of heart failure at least 2.4-fold in men and 5.1-fold in women compared to individuals without diabetes. Despite the increase in the number of cases in the past several decades, the underlying molecular mechanisms of DC pathogenesis remain poorly understood, thereby preventing the development of effective diagnostic tools and pharmacotherapies as well as preventive strategies. One of the emerging hypothesis is that altered membrane polyunsaturated fatty acid composition can activate ER stress signaling, oxidative stress and inflammation in cells. It has been speculated that increased membrane phospholipid saturation may be an underlying cause of many metabolic disorders. Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is a major cardiac enzyme that catalyzes the formation of phosphatidylcholine (PC) from lysophosphatidylcholine. LPCAT3 preferentially synthesizes PC containing unsaturated fatty acids at the sn-2 position. A recent study has shown that LPCAT3 overexpression in livers of obese diabetic db/db mice effectively reduced ER stress by modulating PC saturation. However, the role of LPCAT3 in cardiac metabolism is very poorly understood. Therefore, the proposed project aims at establishing the role of LPCAT3 in cardiac function and investigating the effect that LPCAT3 deficiency may play in development of DC. Additionally, the project will investigate the potential of PC supplemented diet to improve cardiac function in obese mice. Finally, the proposed study will investigate the potential of LPCAT3 overexpression through its transcription factor - liver X receptor (LXR) activation on improving cardiomyocyte structure and function in acute lipotoxicity.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
海外基金