6533b86cfe1ef96bd12c82aa
RESEARCH PRODUCT
Lipid profiling following intake of the Omega 3 fatty acid DHA identifies the peroxidized metabolites F-4-Neuroprostanes as the best predictors of atherosclerosis prevention
Céline DemougeotTheresa L. PedersenJohn W. NewmanThierry DurandCécile GladineOlivier BerdeauxBlandine ComteAndrzej MazurEstelle Pujos-guillotJean-marie Galanosubject
MouseBlood PressureCardiovascularBiochemistryMice0302 clinical medicineTandem Mass SpectrometryAetiologylcsh:Sciencechemistry.chemical_classificationLiquid0303 health sciences[CHIM.ORGA]Chemical Sciences/Organic chemistryFatty Acidsanti-atherogenic;omega 3 fatty acids;epa;dha;bioactive lipid;atherosclerosis;pufas;effects;molecularLipids3. Good healthFatty Acids UnsaturatedMedicinemedicine.medical_specialtyanti-atherogenicKnockoutAortic DiseasesMédecine humaine et pathologieGas Chromatography-Mass SpectrometryLDLDose-Response RelationshipLipid Mediators03 medical and health sciencesomega 3 fatty acids[ CHIM.ORGA ] Chemical Sciences/Organic chemistryacide gras n 3Complementary and Integrative HealtheffectsBiologybioactive lipidDose-Response Relationship DrugPreventionlcsh:RathéroscléroseEPALipid MetabolismPrevention of disease and conditionsmedicine.diseaseEndocrinologychemistryNeuroprostaneslcsh:QHuman health and pathologyBiomarkersand promotion of well-beinglcsh:Medicine030204 cardiovascular system & hematologymedicine.disease_causeOral and gastrointestinalHeart RateReceptorsBlood plasmaCluster Analysis2.1 Biological and endogenous factorsMice KnockoutUnsaturatedChromatographyMultidisciplinaryFatty liverAnimal ModelsDHALiverBiochemistryDocosahexaenoic acidlipids (amino acids peptides and proteins)DrugResearch ArticlePolyunsaturated fatty acidDocosahexaenoic AcidsClinical Research DesignGeneral Science & TechnologyBiologyModel OrganismsInternal medicinemedicineAnimalsNeuroprostanesAnimal Models of Diseasemolecular3.3 Nutrition and chemopreventionOmega 3 fatty acidNutrition030304 developmental biologyAnalysis of Varianceacide docosahexaénoiqueLipid metabolismAtherosclerosis[SDV.AEN] Life Sciences [q-bio]/Food and NutritionReceptors LDLPUFAs[SDV.AEN]Life Sciences [q-bio]/Food and NutritionOxidative stressChromatography Liquiddescription
International audience; The anti-atherogenic effects of omega 3 fatty acids, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are well recognized but the impact of dietary intake on bioactive lipid mediat or profiles remains unclear. Such a profiling effort may offer novel targets for future studies into the mechanism of action of omega 3 fatty acids. The present study aimed to determine the impact of DHA supplementation on the profiles of polyunsaturated fatty acids (PUFA) oxygenated metabolites and to investigate their contribution to therosclerosis prevention. A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical-mediated peroxidation and the increased oxidative stress associated with plaque formation. Atherosclerosis prone mice (LDLR -/-) received increasing doses of DHA (0, 0.1, 1 or 2% of energy) during 20 weeks leading to a dose -dependent reduction of atherosclerosis (R2=0.97, p=0.02), trig lyceridemia (R2=0.97, p=0.01) and cholesterolemia (R2=0.96, p<0.01). Targeted lipidomic analyses revealed that both the profiles of EPA and DHA and their corresponding oxygenated metabolites were substantially modulated in plasma and liver. Notably, the he patic level of F4-neuroprostanes, a specific class of DHA peroxidized metabolites, was strongly correlated with the hepatic DHA level. Moreover, unbiased statistical analysis including correlation analyses, hierarchical cluster and projection to latent structure discriminate analysis revealed that the hepatic level of F4-neuroprostanes was the variable the most negatively correlated with the plaque extent (p<0.001) and along with plasma EPA-derived diols was an important mathematical positive predictor of a therosclerosis revention. Thus, oxygenated n-3 PUFAs, and F4-neuroprostanes in particular, are potential biomarkers of DHA -associated atherosclerosis prevention. While these may contribute to the anti-atherogenic effects of DHA, further in vitro investigations are needed to confirm such a contention and to decipher the molecular mechanisms of action ________________________________
year | journal | country | edition | language |
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2014-02-18 |